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News amp Views Issue 5 September 2015
INDIA ALLIANCE
As we bring out this September issue our Science Communication workshop mentors Drs Lolitika Mandal Mahak
Sharma Anant Bhan Anurag Agrawal and Prof Sandhya Visweswariah conclude the 12th two-day workshop in
Hyderabad
We do not have any updates on the Fellowship front as currently all our fellowship competitions are closed and the
submitted applications are under review In this newsletter some of our Research Training Fellows write about why they
chose to pursue a career in clinical research and how the IA Fellowship scheme will be helpful going forward In our
Public Engagement section we give you an account of our recently concluded DNA70 Public Lecture Series and
announcement for our newly launched bdquoResearch Image competition‟ for Fellows Even though the Monsoon season
passed away quietly our Fellows made sure it rained publications In this issue we also feature recently published
works of our Fellows Drs Bushra Ateeq Sunish Kumar Radhakrishnan Rakesh Kumar Laishram Amit Dutt and Subba Rao
Gangi Setty in the bdquoIA Research Highlights‟ section
In this issue the feature article ldquoPeeking inside the HIV infected cellsrdquo by our Senior Fellow Dr Amit Singh provides
an insightful overview of the research strategies for HIV and TB eradication in the context of his current research Early
Career Fellows Drs Megha and Neha Vyas address the elephant in the room They pose important questions about the
future of postdocs to the scientific community in India in their opinion piece titled ldquoEarly Career Fellow What nextrdquo Dr
Shital Sarah Ahaley our Early Career Fellow at IISER Pune gives an interesting account of the EMBO Lab management
course she attended in Germany which helped her to understand the subtle difference between management and
leadership and reinforced the importance of scientific leadership for a successful research career in a report titled ldquo
Leadership and Management two sides of the same coinrdquo In our interview section we bring to you a very candid
and engaging interview of one our Public Lecture speakers Dr Ajit Varki who is a distinguished professor of medicine
and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University
of California San Diego USA Our Early Career Fellow and newly appointed Assistant Professor at NIMHANS Dr
Urvakhsh Mehta shares with us what inspired him to transition from being an MD to a clinician researcher and what
keeps him going every day in the bdquoFellow in the Spotlight‟ section Last but not the least our Grants Adviser Dr Suveera
Dhup reminisces about her childhood days and tells us why it has been fun to work at the India Alliance in bdquoIA Staff
Corner‟ Also don‟t forget to check the announcements for Clinical training workshop organised by George Institute
and Young Investigator meeting 2016
My heartfelt gratitude goes out to all the contributors for this issue A special thanks to Dr Subba Rao Gangi Setty for
sharing a lovely image for the cover
We will continue to bring to you interesting scientific discoveries and discussions and as always look forward to your
comments and suggestions
Best wishes
Sarah Iqbal
Public Engagement Officer
EDITORIAL
1
CONTENTS
3 RESEARCH TRAINING FELLOWS
5 INDIA ALLIANCE PUBLIC ENGAGEMENT CORNER
Conclusion of DNA70 Public Lecture Series- a report
7 INDIA ALLIANCE RESEARCH HIGHLIGHTS
Featuring recent research articles by Fellows Drs Bushra Ateeq Sunish Kumar
Radhakrishnan Rakesh K Laishram Amit Dutt amp Subba Rao Gangi Setty
11 INDIA ALLIANCE FELLOW IN SPOTLIGHT
Dr Urvakhsh Mehta Early Career Fellow NIMHANS Bangalore
13 FEATURE ARTICLE
ldquoPeeking into the HIV infected cellsrdquo
by Dr Amit Singh Intermediate Fellow IISc Bangalore
15 IN CONVERSATION WITH
Dr Ajit Varki distinguished professor of medicine and cellular and molecular
medicine and co-director of the Glycobiology Research and Training Center at
UCSD
17 VIEWPOINT ldquoEarly Career Fellow What nextrdquo by Drs Megha and Neha Vyas Early Career Fellows at NCBS and inStem Bangalore respectively
19 WORKSHOP ldquoLeadership and management two sides of the same coinrdquo by Dr Shital Sarah Ahaley Early Career Fellows IISER Pune
20 INDIA ALLIANCE STAFF CORNER
Dr Suveera Dhup Grants Adviser India Alliance
21 EXTERNAL EVENTS
2
The Wellcome TrustDBT India Alliancersquos two-year Research Training Fellowship was launched in 2014 and is a first-of-its-kind
programme for clinicians in India This mentored programme is unique in terms of the expectations it has set out for the structure of the training programme and involvement it demands from the research supervisors The provision to get trained under the dual supervision of a clinical and a basic science researcher and the flexibility to attend coursesworkshops allows Clinicians and Allied Health professionals to receive systematic training in research methodology Some of the awarded Fellows from the first round of these Fellowships share their views on this Fellowship and how it will help them in the career paths they have chosen to pursue Click on their images to find out more about their current research projects
INDIA ALLIANCE
RESEARCH TRAINING FELLOWS Clinical and Public Health Research Fellowships
More information on the India Alliance Clinical
and Public Health Fellowships can be found at
httpwellcomedbtorgfellowshiptypeclinical-
and-public-health-research-fellowships
Aiming at a surgical career I was fortunate enough to
get into post-graduation in the subject of Oral and
Maxillofacial Surgery at one of the premier institutes in India
SDM college of Dental Sciences is the first institute in India to
have a dedicated Craniofacial Surgery unit performing over
1500 surgeries every year The patient problems included but
not restricted to oro-facial clefts trauma head and neck
oncology facial esthetic surgeries and infections Facial
trauma remains one of the most common procedures
performed by the maxillofacial surgeons Joining Mazumdar
Shaw Medical Center as a fellow in Cranio-Maxillofacial
Surgery provided me the necessary niche to take this
clinical problem to lab Mazumdar Shaw medical Center
sports a dedicated state-of-the-art research lab facility with
numerous research projects currently underway Professor
Dr Paul C Salins the Chief of Cranio-Maxillofacial Services
and Medical Director of the hospital encouraged me to
take up basic science research in this field Dr Aditya
Chaubey the Chief Scientific Officer of Mazumdar Shaw
Centre for Translational Research who has been working
extensively in the field of stem cells and has already
developed excellent in vivo models for bone regeneration
and scaffold designing accepted to guide me in starting a
research career I feel this research training fellowship will
allow me to dedicate my time in this exciting field and may
in fact allow me to pursue a translational research career in
the future Though inexperienced I believe that undertaking
this fellowship at an early stage of my career will help me in
better understanding of the existing clinical problems and
developing a scientific problem solving attitude and apply
the newly acquired skills in patient care
Dr Muralidhara Nagarjuna Mazumdar Shaw Center for
Translational Research
Bangalore
Training in the prestigious Bangalore Medical College and
Research Institute gave me a strong foundation in clinical
medicine I stood 1st for the state in the UG Medical Karnataka
Common Entrance Test Right from the early days of MBBS I
was fascinated by a career in a field that involves treatment
and research of neuropsychiatric disorders I consider myself
privileged to have obtained MD Psychiatry at NIMHANS which
is a premiere multidisciplinary academic research and health
care institute in Brain - Mind - Behaviour Axis in India I
developed a keen interest in addiction psychiatry and did my
MD thesis dissertation and also a post-doctoral addiction
psychiatry clinical fellowship under the guidance of Dr Vivek
Benegal During this time I also trained myself in advanced
neuro-imaging analysis under the expertise of Dr G
Venkatasubramanian
Now I want to pursue a career of a clinician scientist and
train myself in basic science I have been fortunate that Dr
Ravi Muddashetty has kindly agreed to train me at molecular
genetics laboratory at inStem NCBS under this fellowship
Currently I am also pursuing PhD in Psychiatry at NIMHANS
During this proposed research I wish to further elucidate the
biopsychosocial vulnerabilities for substance misuse in alcohol
naive children from multiplex alcohol-dependence families
using Imaging-genomics approach
The RTF has provided the right platform for a young
clinician like me I hope to continue with translational research
and clinical work as an independent investigator the field of
neuroimaging and psychiatric genetics with expertise in
alcoholism
Dr Bharat Holla NIMHANS Bangalore
3
Medicine was an automatic career choice for me as no
other profession can boast of doing social good while
challenging one academically and giving one a sense of
purpose The choice of specializing in pathology was
spontaneous for apart from providing answers to my curious
questions on the why‟s and how‟s of most diseases it is a
subject so full of color and at times so full of instant satisfaction
besides providing scope for teaching and research which I
wish to be very actively involved in
The research projects I have taken up so far (through
MBBS Internship and MD thesis) have given me a small glimpse
into the world of research and have motivated me enough to
want to pursue a research based approach in my practice of
Pathology With this background after completing my MD
studies joining St John‟s as Lecturer of Pathology in 2013 was
an instinctive decision for apart from the pleasant work
environment it nurtures budding researchers through many
inspiring clinicians like my principle supervisor Dr Usha Kini
Having worked with her team on the diagnostics aspects of
Hirschsprung disease over the past 2 years we are now
studying the molecular aspects of the disease Realising the
need to tie up with a molecular biologist I now work in Dr
Sudhir Krishna‟s lab at the National Institute of Biological
Sciences where I am learning the various molecular
principles and techniques to carry out the proposed
research
My pursuit to learn and implement molecular biology in
Medicine took me to the Molecular Medicine unit head at
St John‟s who told me that in order to fulfill my quest I need
3 things 1 an interest to learn molecular biology 2
adequate time to learn (1 hour per day after clinical work
would not suffice) and 3 the financial resource to access
these techniques As a pathologist my interest in molecular
biology stemmed from the calling to go beyond
morphological diagnosis to understanding the projections of
molecular alterations that drive disease into the realm of
morphology And although morphological diagnosis is
challenging in itself I wanted to use my two-dimensional
morphological view of disease as a gateway to understand
the three (and higher) dimensional molecular world of
disease much of which may appear difficult to interpret but
never the less is the need of the hour to provide
personalized therapies to our patients It was along this track
that I came across this India Alliance RTF which would not
only provide me the financial resource but above all the
protected time to learn and apply the various molecular
techniques while still retaining my feet in clinical medicine
Dr Maria Frances Bukelo St Johnrsquos Medical College Bangalore
Dr Sanjay K Chilbule Christian Medical College Vellore
After fellowship in paediatric orthopaedics at CMC
Vellore under supervision of Dr Vrisha Madhuri I joined one
of her research project to design the compliance monitored
clubfoot brace (Padma Pada) in collaboration with
engineers from IISc Bangalore It was quite inspiring to see
the replacement of age old brace by newer better and
comfortable brace which parents are not ready to let of
due to its definite advantage for child This was possible due
to Dr Vrisha‟s scientific disposition and the fact that clinician
themselves with the help of collaborators can bring in the
changes in the patient management adapting the research
in their prospectus
While working with Dr Vrisha‟s for cartilage and bone
regeneration involving human and animal experiments we
started to extend our thinking to one more field Outcome of
the osteosarcoma (OS) which is a commonest bone tumour
in children is not very favorable due to heterogeneity and
variable response to chemotherapy With availability of
patients and advanced laboratory in same unit we started
exploring this field initially with collaboration with
radiotherapy and medical oncology units at CMC Vellore In
literature we found out that most of the CSC research work
done for OS is being done on cell lines We started working
on cancer stem cells (CSCs) from osteosarcoma tissue from
patients with definite aim of translating this knowledge for
management of the osteosarcoma in future
In addition of learning all the bench work related to
planned work the Research Training Fellowship is providing
the unique opportunity to a clinician like me to be part of
basic science arena and to be able to develop a scientific
temperament This RTF is definitely metamorphosing the
thinking process to apply the basic science for the
orthopaedic disorders and to opt research as a career
continuing the clinical work
The Wellcome TrustDBT India Alliance
RESEARCH TRAINING FELLOWS
4
INDIA ALLIANCE
PUBLIC ENGAGEMENT CORNER
DNA70 Public Lecture Series
India Alliance organises several public lectures at various institutions across India to give those interested in science an opportunity to interact with eminent scientists from around the
world
In 1944 Oswald Avery together with Colin MacLeod and
Maclyn McCarty made the landmark discovery that
deoxyribonucleic acid (DNA) and not proteins carry genetic
information and is therefore the basis of inheritance In the 70
years since Avery‟s discovery DNA has come a long way
India Alliance celebrated the discovery of DNA as a
hereditary molecule through a series of public lectures in
various cities in 2014-15 given by researchers who have done
pioneering work centered around the DNA molecule The four
lectures in this series were given by Prof W Ian Lipkin (Center
for Infection and Immunity Mailman School of Public Health
Columbia University USA) and Prof Nadrian Seeman
(Margaret and Herman Sokol Professor of Chemistry New York
University USA) Dr Karen Nelson (President J Craig Venter
Institute Rockville USA) and Prof Shankar Balasubramanian
(University of Cambridge UK)
Our first speaker in this series Prof W Ian Lipkin a well-known
expert on the use of molecular methods for pathogen
discovery gave a lecture titled ldquoBad bugs on the big screen
science fiction and fact in Hollywoodrdquo in New Delhi discussed
how filmmakers often mix fact with fiction when dealing with
science stories whereas his second talk ldquoSmall Game Hunting
disease control in the genome erardquo in Bangalore provided a
comprehensive review of pathogen discovery microbiome
research and zoonotic diseases Our second speaker in this
series inventor of the field of DNA Nanotechnology Dr
Nadrian Seeman gave lectures in New Delhi Hyderabad
Kolkata and Shantiniketan where his talks on structural DNA
nanotechnology received very many questions from both
eager scientists and curious nonscientists The third lecture in
this series given by Dr Karen Nelson focused on the human
microbiome emerging infectious diseases and implications of
both for human health which was very aptly titled ldquoThe Zoo in
Yourdquo The last lecture in the DNA70 Public Lecture Series was
given by Prof Shankar Balasubramanian of University of
Cambridge co-inventor of next generation genome
sequencing technology and co-founder of the company
Solexa His lecture ldquoDecoding Human Genome on a
population scalerdquo discussed the history of DNA sequencing
the method that was developed by him and his colleagues at
Cambridge University for rapidly decoding genomes and the
impact of these technologies on life sciences medicine and
society For those of you who missed his lectures in Delhi and
Bangalore here‟s a short report
Report Prof Balasubramanian‟s lecture began with a humble
yet engaging account of his scientific beginnings in the
Department of Chemistry at University of Cambridge
followed by his successful association with another chemist Dr
David Klenerman along with whom he developed the
genome sequencing technology He described how
5
contributions of various scientists in elucidating the DNA
code- one of them being the father of genomics Fred
Sanger- influenced and shaped his work in this field He
recounted how they accidently invented this
technology as what they had really set out to study was
the motion of the DNA polymerase as it synthesised a
single DNA molecule using fluorescent tagging He
took the audience through the chemical processes of
DNA polymerisation and how his lab exploited these
processes to attach a fluorescent molecule on the
nucleic acid bases which enabled them to visualize the
different bases in a DNA molecule This chemistry was
then employed to develop the sequencing technology
which is now being commercialized by Illumina after it
acquired the company Solexa originally formed by Drs
Balasubramanian and Klenerman in 1998 During his talk
at IISc Bangalore Prof Balasubramanian admitted that
the practical question of how the information derived
from the Human Genome Project can be made useful
in comparing genomes from different individuals
inspired him to invent this quick method of DNA
sequencing Towards the end of the lecture Prof
Balasubramanian described a few incidents where his
method of sequencing had been useful for physicians to
perform diagnosis and develop personalised therapies
to treat patients
He acknowledged among others the support of the
UK funding body BBSRC for giving wings to their idea
when it was in its most naiumlve and nascent stage almost
20 years ago
Both the lectures were followed by an engaging
QampA session with an audience of more than 250 in
attendance at both venues which covered scientific
ethical sociological and commercial aspects of the
genome sequencing technology Some of the questions
raised at the session intended to discuss the impact of
genome sequencing on society genome of a
bdquoperfectly‟ healthy individual future of epigenome and
protein sequencing and possibility of reducing the cost
of the existing sequencing technologies for which Prof
Balasubramanian offered optimistic but practical
answers Apart from senior scientists the audience
mainly comprised of young students and researchers
who continued to interact enthusiastically with the
speaker well after the talk was over
Public Engagement Competition for India Alliance Fellows
To enable our Fellows to effectively and creatively engage with the
society about biomedical science we announced the first rolling bdquoPublic
Engagement competition‟ in May 2014 This competition is a valuable
opportunity for our Fellows to showcase and share their Science with the
Public and collaborate with other members of the society The
engagement can be through research social activities teaching arts
moviesdocumentary and other modes of knowledge sharing with the
central goal of educating and improving public awareness of science
and human health issues To apply please download the application
form here and send the completed application form to
publicengagementwellcomedbtorg
Image Competition for India Alliance Fellows
We are pleased to announce the launch of the Research Image
Competition for our Fellows where we invite you to submit images related
to biomedical research and healthcare Images could include
photographs clinical amp scientific images hand-drawn illustrations
Images must convey a scientific principle or a relevant human health
perspective Images can be produced by individuals or by a team
However the Fellow has to play a key role in the production of the
image Images can be submitted for both science and human health
categories but only two for each category will be allowed
Submitting the images Email your high-quality image with an easy-to-
understand description and a short image title to
publicengagementwellcomedbtorg Please mention the names of all
the people who were involved in producing the image
Deadline to submit images 15 October 2015
DNA70 Public Lecture Series
6
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Colorectal cancer (CRC) is the third most commonly
diagnosed cancer type approximately one million individuals
worldwide are diagnosed with the disease each year Anti-
epidermal growth factor receptor (EGFR) therapies such as
monoclonal antibody (cetuximab) against EGFR are either
administered as part of first-line treatment or as a final option
when other treatments fail However half of the CRC patients
who harbor mutations in KRAS NRAS and BRAF genes acquire
resistance to anti-EGFR drugs thus highlighting the necessity
for additional targeted therapies In the current study we
have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)
is highly expressed among CRC patients and demonstrated
the functional significance of SPINK1 in disease progression
and metastases SPINK1 over-expression in CRC has been
associated with advanced stage of the disease poor clinical
outcome and metastasis to liver
We have shown that silencing SPINK1 in BRAF mutation
positive WiDr colon adenocarcinoma cells demonstrate
decrease in cell proliferation invasion soft agar colony
formation and reduced tumor growth and distant metastases
in in-vivo model systems Importantly SPINK1 silencing led to
up-regulation of various metallothionein isoforms considered
as tumor suppressors in CRC which confers sensitivity to
chemotherapeutic drug doxorubicin Taken together our
findings strengthen the rationale for using the combinatorial
treatment approach for the SPINK1-positive CRC patients Our
study also demonstrates an important role for the SPINK1 over-
expression in CRC disease progression a phenomenon that
needs careful evaluation towards effective therapeutic target
development
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression R Tiwari S K Pandey S Goel V Bhatia S Shukla X Jing S M Dhanasekaran and B Ateeq Oncogenesis (2015)
Image SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin
Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins
expression DR BUSHRA ATEEQ Intermediate Fellow IIT Kanpur
Signal regulation at the mRNA 3rsquo-end Role of Phosphorylation Phosphorylation regulates gene specificity
DR RAKESH SINGH LAISHRAM Intermediate Fellow Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram
Gene expression in humans involves multiple steps from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP)
Poly(A) tail is essential for stability and efficient translation of
the mRNA Star-PAP is a non-canonical PAP that selects mRNA
target for polyadenylation Star-PAP together with co-
regulator PIPKIα controls expression of genes involved in
oxidative stress response and apoptosis We showed that
phosphorylation of Star-PAP determines specificity of its target
gene expressions downstream of signaling pathways
7
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
As we bring out this September issue our Science Communication workshop mentors Drs Lolitika Mandal Mahak
Sharma Anant Bhan Anurag Agrawal and Prof Sandhya Visweswariah conclude the 12th two-day workshop in
Hyderabad
We do not have any updates on the Fellowship front as currently all our fellowship competitions are closed and the
submitted applications are under review In this newsletter some of our Research Training Fellows write about why they
chose to pursue a career in clinical research and how the IA Fellowship scheme will be helpful going forward In our
Public Engagement section we give you an account of our recently concluded DNA70 Public Lecture Series and
announcement for our newly launched bdquoResearch Image competition‟ for Fellows Even though the Monsoon season
passed away quietly our Fellows made sure it rained publications In this issue we also feature recently published
works of our Fellows Drs Bushra Ateeq Sunish Kumar Radhakrishnan Rakesh Kumar Laishram Amit Dutt and Subba Rao
Gangi Setty in the bdquoIA Research Highlights‟ section
In this issue the feature article ldquoPeeking inside the HIV infected cellsrdquo by our Senior Fellow Dr Amit Singh provides
an insightful overview of the research strategies for HIV and TB eradication in the context of his current research Early
Career Fellows Drs Megha and Neha Vyas address the elephant in the room They pose important questions about the
future of postdocs to the scientific community in India in their opinion piece titled ldquoEarly Career Fellow What nextrdquo Dr
Shital Sarah Ahaley our Early Career Fellow at IISER Pune gives an interesting account of the EMBO Lab management
course she attended in Germany which helped her to understand the subtle difference between management and
leadership and reinforced the importance of scientific leadership for a successful research career in a report titled ldquo
Leadership and Management two sides of the same coinrdquo In our interview section we bring to you a very candid
and engaging interview of one our Public Lecture speakers Dr Ajit Varki who is a distinguished professor of medicine
and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University
of California San Diego USA Our Early Career Fellow and newly appointed Assistant Professor at NIMHANS Dr
Urvakhsh Mehta shares with us what inspired him to transition from being an MD to a clinician researcher and what
keeps him going every day in the bdquoFellow in the Spotlight‟ section Last but not the least our Grants Adviser Dr Suveera
Dhup reminisces about her childhood days and tells us why it has been fun to work at the India Alliance in bdquoIA Staff
Corner‟ Also don‟t forget to check the announcements for Clinical training workshop organised by George Institute
and Young Investigator meeting 2016
My heartfelt gratitude goes out to all the contributors for this issue A special thanks to Dr Subba Rao Gangi Setty for
sharing a lovely image for the cover
We will continue to bring to you interesting scientific discoveries and discussions and as always look forward to your
comments and suggestions
Best wishes
Sarah Iqbal
Public Engagement Officer
EDITORIAL
1
CONTENTS
3 RESEARCH TRAINING FELLOWS
5 INDIA ALLIANCE PUBLIC ENGAGEMENT CORNER
Conclusion of DNA70 Public Lecture Series- a report
7 INDIA ALLIANCE RESEARCH HIGHLIGHTS
Featuring recent research articles by Fellows Drs Bushra Ateeq Sunish Kumar
Radhakrishnan Rakesh K Laishram Amit Dutt amp Subba Rao Gangi Setty
11 INDIA ALLIANCE FELLOW IN SPOTLIGHT
Dr Urvakhsh Mehta Early Career Fellow NIMHANS Bangalore
13 FEATURE ARTICLE
ldquoPeeking into the HIV infected cellsrdquo
by Dr Amit Singh Intermediate Fellow IISc Bangalore
15 IN CONVERSATION WITH
Dr Ajit Varki distinguished professor of medicine and cellular and molecular
medicine and co-director of the Glycobiology Research and Training Center at
UCSD
17 VIEWPOINT ldquoEarly Career Fellow What nextrdquo by Drs Megha and Neha Vyas Early Career Fellows at NCBS and inStem Bangalore respectively
19 WORKSHOP ldquoLeadership and management two sides of the same coinrdquo by Dr Shital Sarah Ahaley Early Career Fellows IISER Pune
20 INDIA ALLIANCE STAFF CORNER
Dr Suveera Dhup Grants Adviser India Alliance
21 EXTERNAL EVENTS
2
The Wellcome TrustDBT India Alliancersquos two-year Research Training Fellowship was launched in 2014 and is a first-of-its-kind
programme for clinicians in India This mentored programme is unique in terms of the expectations it has set out for the structure of the training programme and involvement it demands from the research supervisors The provision to get trained under the dual supervision of a clinical and a basic science researcher and the flexibility to attend coursesworkshops allows Clinicians and Allied Health professionals to receive systematic training in research methodology Some of the awarded Fellows from the first round of these Fellowships share their views on this Fellowship and how it will help them in the career paths they have chosen to pursue Click on their images to find out more about their current research projects
INDIA ALLIANCE
RESEARCH TRAINING FELLOWS Clinical and Public Health Research Fellowships
More information on the India Alliance Clinical
and Public Health Fellowships can be found at
httpwellcomedbtorgfellowshiptypeclinical-
and-public-health-research-fellowships
Aiming at a surgical career I was fortunate enough to
get into post-graduation in the subject of Oral and
Maxillofacial Surgery at one of the premier institutes in India
SDM college of Dental Sciences is the first institute in India to
have a dedicated Craniofacial Surgery unit performing over
1500 surgeries every year The patient problems included but
not restricted to oro-facial clefts trauma head and neck
oncology facial esthetic surgeries and infections Facial
trauma remains one of the most common procedures
performed by the maxillofacial surgeons Joining Mazumdar
Shaw Medical Center as a fellow in Cranio-Maxillofacial
Surgery provided me the necessary niche to take this
clinical problem to lab Mazumdar Shaw medical Center
sports a dedicated state-of-the-art research lab facility with
numerous research projects currently underway Professor
Dr Paul C Salins the Chief of Cranio-Maxillofacial Services
and Medical Director of the hospital encouraged me to
take up basic science research in this field Dr Aditya
Chaubey the Chief Scientific Officer of Mazumdar Shaw
Centre for Translational Research who has been working
extensively in the field of stem cells and has already
developed excellent in vivo models for bone regeneration
and scaffold designing accepted to guide me in starting a
research career I feel this research training fellowship will
allow me to dedicate my time in this exciting field and may
in fact allow me to pursue a translational research career in
the future Though inexperienced I believe that undertaking
this fellowship at an early stage of my career will help me in
better understanding of the existing clinical problems and
developing a scientific problem solving attitude and apply
the newly acquired skills in patient care
Dr Muralidhara Nagarjuna Mazumdar Shaw Center for
Translational Research
Bangalore
Training in the prestigious Bangalore Medical College and
Research Institute gave me a strong foundation in clinical
medicine I stood 1st for the state in the UG Medical Karnataka
Common Entrance Test Right from the early days of MBBS I
was fascinated by a career in a field that involves treatment
and research of neuropsychiatric disorders I consider myself
privileged to have obtained MD Psychiatry at NIMHANS which
is a premiere multidisciplinary academic research and health
care institute in Brain - Mind - Behaviour Axis in India I
developed a keen interest in addiction psychiatry and did my
MD thesis dissertation and also a post-doctoral addiction
psychiatry clinical fellowship under the guidance of Dr Vivek
Benegal During this time I also trained myself in advanced
neuro-imaging analysis under the expertise of Dr G
Venkatasubramanian
Now I want to pursue a career of a clinician scientist and
train myself in basic science I have been fortunate that Dr
Ravi Muddashetty has kindly agreed to train me at molecular
genetics laboratory at inStem NCBS under this fellowship
Currently I am also pursuing PhD in Psychiatry at NIMHANS
During this proposed research I wish to further elucidate the
biopsychosocial vulnerabilities for substance misuse in alcohol
naive children from multiplex alcohol-dependence families
using Imaging-genomics approach
The RTF has provided the right platform for a young
clinician like me I hope to continue with translational research
and clinical work as an independent investigator the field of
neuroimaging and psychiatric genetics with expertise in
alcoholism
Dr Bharat Holla NIMHANS Bangalore
3
Medicine was an automatic career choice for me as no
other profession can boast of doing social good while
challenging one academically and giving one a sense of
purpose The choice of specializing in pathology was
spontaneous for apart from providing answers to my curious
questions on the why‟s and how‟s of most diseases it is a
subject so full of color and at times so full of instant satisfaction
besides providing scope for teaching and research which I
wish to be very actively involved in
The research projects I have taken up so far (through
MBBS Internship and MD thesis) have given me a small glimpse
into the world of research and have motivated me enough to
want to pursue a research based approach in my practice of
Pathology With this background after completing my MD
studies joining St John‟s as Lecturer of Pathology in 2013 was
an instinctive decision for apart from the pleasant work
environment it nurtures budding researchers through many
inspiring clinicians like my principle supervisor Dr Usha Kini
Having worked with her team on the diagnostics aspects of
Hirschsprung disease over the past 2 years we are now
studying the molecular aspects of the disease Realising the
need to tie up with a molecular biologist I now work in Dr
Sudhir Krishna‟s lab at the National Institute of Biological
Sciences where I am learning the various molecular
principles and techniques to carry out the proposed
research
My pursuit to learn and implement molecular biology in
Medicine took me to the Molecular Medicine unit head at
St John‟s who told me that in order to fulfill my quest I need
3 things 1 an interest to learn molecular biology 2
adequate time to learn (1 hour per day after clinical work
would not suffice) and 3 the financial resource to access
these techniques As a pathologist my interest in molecular
biology stemmed from the calling to go beyond
morphological diagnosis to understanding the projections of
molecular alterations that drive disease into the realm of
morphology And although morphological diagnosis is
challenging in itself I wanted to use my two-dimensional
morphological view of disease as a gateway to understand
the three (and higher) dimensional molecular world of
disease much of which may appear difficult to interpret but
never the less is the need of the hour to provide
personalized therapies to our patients It was along this track
that I came across this India Alliance RTF which would not
only provide me the financial resource but above all the
protected time to learn and apply the various molecular
techniques while still retaining my feet in clinical medicine
Dr Maria Frances Bukelo St Johnrsquos Medical College Bangalore
Dr Sanjay K Chilbule Christian Medical College Vellore
After fellowship in paediatric orthopaedics at CMC
Vellore under supervision of Dr Vrisha Madhuri I joined one
of her research project to design the compliance monitored
clubfoot brace (Padma Pada) in collaboration with
engineers from IISc Bangalore It was quite inspiring to see
the replacement of age old brace by newer better and
comfortable brace which parents are not ready to let of
due to its definite advantage for child This was possible due
to Dr Vrisha‟s scientific disposition and the fact that clinician
themselves with the help of collaborators can bring in the
changes in the patient management adapting the research
in their prospectus
While working with Dr Vrisha‟s for cartilage and bone
regeneration involving human and animal experiments we
started to extend our thinking to one more field Outcome of
the osteosarcoma (OS) which is a commonest bone tumour
in children is not very favorable due to heterogeneity and
variable response to chemotherapy With availability of
patients and advanced laboratory in same unit we started
exploring this field initially with collaboration with
radiotherapy and medical oncology units at CMC Vellore In
literature we found out that most of the CSC research work
done for OS is being done on cell lines We started working
on cancer stem cells (CSCs) from osteosarcoma tissue from
patients with definite aim of translating this knowledge for
management of the osteosarcoma in future
In addition of learning all the bench work related to
planned work the Research Training Fellowship is providing
the unique opportunity to a clinician like me to be part of
basic science arena and to be able to develop a scientific
temperament This RTF is definitely metamorphosing the
thinking process to apply the basic science for the
orthopaedic disorders and to opt research as a career
continuing the clinical work
The Wellcome TrustDBT India Alliance
RESEARCH TRAINING FELLOWS
4
INDIA ALLIANCE
PUBLIC ENGAGEMENT CORNER
DNA70 Public Lecture Series
India Alliance organises several public lectures at various institutions across India to give those interested in science an opportunity to interact with eminent scientists from around the
world
In 1944 Oswald Avery together with Colin MacLeod and
Maclyn McCarty made the landmark discovery that
deoxyribonucleic acid (DNA) and not proteins carry genetic
information and is therefore the basis of inheritance In the 70
years since Avery‟s discovery DNA has come a long way
India Alliance celebrated the discovery of DNA as a
hereditary molecule through a series of public lectures in
various cities in 2014-15 given by researchers who have done
pioneering work centered around the DNA molecule The four
lectures in this series were given by Prof W Ian Lipkin (Center
for Infection and Immunity Mailman School of Public Health
Columbia University USA) and Prof Nadrian Seeman
(Margaret and Herman Sokol Professor of Chemistry New York
University USA) Dr Karen Nelson (President J Craig Venter
Institute Rockville USA) and Prof Shankar Balasubramanian
(University of Cambridge UK)
Our first speaker in this series Prof W Ian Lipkin a well-known
expert on the use of molecular methods for pathogen
discovery gave a lecture titled ldquoBad bugs on the big screen
science fiction and fact in Hollywoodrdquo in New Delhi discussed
how filmmakers often mix fact with fiction when dealing with
science stories whereas his second talk ldquoSmall Game Hunting
disease control in the genome erardquo in Bangalore provided a
comprehensive review of pathogen discovery microbiome
research and zoonotic diseases Our second speaker in this
series inventor of the field of DNA Nanotechnology Dr
Nadrian Seeman gave lectures in New Delhi Hyderabad
Kolkata and Shantiniketan where his talks on structural DNA
nanotechnology received very many questions from both
eager scientists and curious nonscientists The third lecture in
this series given by Dr Karen Nelson focused on the human
microbiome emerging infectious diseases and implications of
both for human health which was very aptly titled ldquoThe Zoo in
Yourdquo The last lecture in the DNA70 Public Lecture Series was
given by Prof Shankar Balasubramanian of University of
Cambridge co-inventor of next generation genome
sequencing technology and co-founder of the company
Solexa His lecture ldquoDecoding Human Genome on a
population scalerdquo discussed the history of DNA sequencing
the method that was developed by him and his colleagues at
Cambridge University for rapidly decoding genomes and the
impact of these technologies on life sciences medicine and
society For those of you who missed his lectures in Delhi and
Bangalore here‟s a short report
Report Prof Balasubramanian‟s lecture began with a humble
yet engaging account of his scientific beginnings in the
Department of Chemistry at University of Cambridge
followed by his successful association with another chemist Dr
David Klenerman along with whom he developed the
genome sequencing technology He described how
5
contributions of various scientists in elucidating the DNA
code- one of them being the father of genomics Fred
Sanger- influenced and shaped his work in this field He
recounted how they accidently invented this
technology as what they had really set out to study was
the motion of the DNA polymerase as it synthesised a
single DNA molecule using fluorescent tagging He
took the audience through the chemical processes of
DNA polymerisation and how his lab exploited these
processes to attach a fluorescent molecule on the
nucleic acid bases which enabled them to visualize the
different bases in a DNA molecule This chemistry was
then employed to develop the sequencing technology
which is now being commercialized by Illumina after it
acquired the company Solexa originally formed by Drs
Balasubramanian and Klenerman in 1998 During his talk
at IISc Bangalore Prof Balasubramanian admitted that
the practical question of how the information derived
from the Human Genome Project can be made useful
in comparing genomes from different individuals
inspired him to invent this quick method of DNA
sequencing Towards the end of the lecture Prof
Balasubramanian described a few incidents where his
method of sequencing had been useful for physicians to
perform diagnosis and develop personalised therapies
to treat patients
He acknowledged among others the support of the
UK funding body BBSRC for giving wings to their idea
when it was in its most naiumlve and nascent stage almost
20 years ago
Both the lectures were followed by an engaging
QampA session with an audience of more than 250 in
attendance at both venues which covered scientific
ethical sociological and commercial aspects of the
genome sequencing technology Some of the questions
raised at the session intended to discuss the impact of
genome sequencing on society genome of a
bdquoperfectly‟ healthy individual future of epigenome and
protein sequencing and possibility of reducing the cost
of the existing sequencing technologies for which Prof
Balasubramanian offered optimistic but practical
answers Apart from senior scientists the audience
mainly comprised of young students and researchers
who continued to interact enthusiastically with the
speaker well after the talk was over
Public Engagement Competition for India Alliance Fellows
To enable our Fellows to effectively and creatively engage with the
society about biomedical science we announced the first rolling bdquoPublic
Engagement competition‟ in May 2014 This competition is a valuable
opportunity for our Fellows to showcase and share their Science with the
Public and collaborate with other members of the society The
engagement can be through research social activities teaching arts
moviesdocumentary and other modes of knowledge sharing with the
central goal of educating and improving public awareness of science
and human health issues To apply please download the application
form here and send the completed application form to
publicengagementwellcomedbtorg
Image Competition for India Alliance Fellows
We are pleased to announce the launch of the Research Image
Competition for our Fellows where we invite you to submit images related
to biomedical research and healthcare Images could include
photographs clinical amp scientific images hand-drawn illustrations
Images must convey a scientific principle or a relevant human health
perspective Images can be produced by individuals or by a team
However the Fellow has to play a key role in the production of the
image Images can be submitted for both science and human health
categories but only two for each category will be allowed
Submitting the images Email your high-quality image with an easy-to-
understand description and a short image title to
publicengagementwellcomedbtorg Please mention the names of all
the people who were involved in producing the image
Deadline to submit images 15 October 2015
DNA70 Public Lecture Series
6
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Colorectal cancer (CRC) is the third most commonly
diagnosed cancer type approximately one million individuals
worldwide are diagnosed with the disease each year Anti-
epidermal growth factor receptor (EGFR) therapies such as
monoclonal antibody (cetuximab) against EGFR are either
administered as part of first-line treatment or as a final option
when other treatments fail However half of the CRC patients
who harbor mutations in KRAS NRAS and BRAF genes acquire
resistance to anti-EGFR drugs thus highlighting the necessity
for additional targeted therapies In the current study we
have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)
is highly expressed among CRC patients and demonstrated
the functional significance of SPINK1 in disease progression
and metastases SPINK1 over-expression in CRC has been
associated with advanced stage of the disease poor clinical
outcome and metastasis to liver
We have shown that silencing SPINK1 in BRAF mutation
positive WiDr colon adenocarcinoma cells demonstrate
decrease in cell proliferation invasion soft agar colony
formation and reduced tumor growth and distant metastases
in in-vivo model systems Importantly SPINK1 silencing led to
up-regulation of various metallothionein isoforms considered
as tumor suppressors in CRC which confers sensitivity to
chemotherapeutic drug doxorubicin Taken together our
findings strengthen the rationale for using the combinatorial
treatment approach for the SPINK1-positive CRC patients Our
study also demonstrates an important role for the SPINK1 over-
expression in CRC disease progression a phenomenon that
needs careful evaluation towards effective therapeutic target
development
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression R Tiwari S K Pandey S Goel V Bhatia S Shukla X Jing S M Dhanasekaran and B Ateeq Oncogenesis (2015)
Image SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin
Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins
expression DR BUSHRA ATEEQ Intermediate Fellow IIT Kanpur
Signal regulation at the mRNA 3rsquo-end Role of Phosphorylation Phosphorylation regulates gene specificity
DR RAKESH SINGH LAISHRAM Intermediate Fellow Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram
Gene expression in humans involves multiple steps from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP)
Poly(A) tail is essential for stability and efficient translation of
the mRNA Star-PAP is a non-canonical PAP that selects mRNA
target for polyadenylation Star-PAP together with co-
regulator PIPKIα controls expression of genes involved in
oxidative stress response and apoptosis We showed that
phosphorylation of Star-PAP determines specificity of its target
gene expressions downstream of signaling pathways
7
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
CONTENTS
3 RESEARCH TRAINING FELLOWS
5 INDIA ALLIANCE PUBLIC ENGAGEMENT CORNER
Conclusion of DNA70 Public Lecture Series- a report
7 INDIA ALLIANCE RESEARCH HIGHLIGHTS
Featuring recent research articles by Fellows Drs Bushra Ateeq Sunish Kumar
Radhakrishnan Rakesh K Laishram Amit Dutt amp Subba Rao Gangi Setty
11 INDIA ALLIANCE FELLOW IN SPOTLIGHT
Dr Urvakhsh Mehta Early Career Fellow NIMHANS Bangalore
13 FEATURE ARTICLE
ldquoPeeking into the HIV infected cellsrdquo
by Dr Amit Singh Intermediate Fellow IISc Bangalore
15 IN CONVERSATION WITH
Dr Ajit Varki distinguished professor of medicine and cellular and molecular
medicine and co-director of the Glycobiology Research and Training Center at
UCSD
17 VIEWPOINT ldquoEarly Career Fellow What nextrdquo by Drs Megha and Neha Vyas Early Career Fellows at NCBS and inStem Bangalore respectively
19 WORKSHOP ldquoLeadership and management two sides of the same coinrdquo by Dr Shital Sarah Ahaley Early Career Fellows IISER Pune
20 INDIA ALLIANCE STAFF CORNER
Dr Suveera Dhup Grants Adviser India Alliance
21 EXTERNAL EVENTS
2
The Wellcome TrustDBT India Alliancersquos two-year Research Training Fellowship was launched in 2014 and is a first-of-its-kind
programme for clinicians in India This mentored programme is unique in terms of the expectations it has set out for the structure of the training programme and involvement it demands from the research supervisors The provision to get trained under the dual supervision of a clinical and a basic science researcher and the flexibility to attend coursesworkshops allows Clinicians and Allied Health professionals to receive systematic training in research methodology Some of the awarded Fellows from the first round of these Fellowships share their views on this Fellowship and how it will help them in the career paths they have chosen to pursue Click on their images to find out more about their current research projects
INDIA ALLIANCE
RESEARCH TRAINING FELLOWS Clinical and Public Health Research Fellowships
More information on the India Alliance Clinical
and Public Health Fellowships can be found at
httpwellcomedbtorgfellowshiptypeclinical-
and-public-health-research-fellowships
Aiming at a surgical career I was fortunate enough to
get into post-graduation in the subject of Oral and
Maxillofacial Surgery at one of the premier institutes in India
SDM college of Dental Sciences is the first institute in India to
have a dedicated Craniofacial Surgery unit performing over
1500 surgeries every year The patient problems included but
not restricted to oro-facial clefts trauma head and neck
oncology facial esthetic surgeries and infections Facial
trauma remains one of the most common procedures
performed by the maxillofacial surgeons Joining Mazumdar
Shaw Medical Center as a fellow in Cranio-Maxillofacial
Surgery provided me the necessary niche to take this
clinical problem to lab Mazumdar Shaw medical Center
sports a dedicated state-of-the-art research lab facility with
numerous research projects currently underway Professor
Dr Paul C Salins the Chief of Cranio-Maxillofacial Services
and Medical Director of the hospital encouraged me to
take up basic science research in this field Dr Aditya
Chaubey the Chief Scientific Officer of Mazumdar Shaw
Centre for Translational Research who has been working
extensively in the field of stem cells and has already
developed excellent in vivo models for bone regeneration
and scaffold designing accepted to guide me in starting a
research career I feel this research training fellowship will
allow me to dedicate my time in this exciting field and may
in fact allow me to pursue a translational research career in
the future Though inexperienced I believe that undertaking
this fellowship at an early stage of my career will help me in
better understanding of the existing clinical problems and
developing a scientific problem solving attitude and apply
the newly acquired skills in patient care
Dr Muralidhara Nagarjuna Mazumdar Shaw Center for
Translational Research
Bangalore
Training in the prestigious Bangalore Medical College and
Research Institute gave me a strong foundation in clinical
medicine I stood 1st for the state in the UG Medical Karnataka
Common Entrance Test Right from the early days of MBBS I
was fascinated by a career in a field that involves treatment
and research of neuropsychiatric disorders I consider myself
privileged to have obtained MD Psychiatry at NIMHANS which
is a premiere multidisciplinary academic research and health
care institute in Brain - Mind - Behaviour Axis in India I
developed a keen interest in addiction psychiatry and did my
MD thesis dissertation and also a post-doctoral addiction
psychiatry clinical fellowship under the guidance of Dr Vivek
Benegal During this time I also trained myself in advanced
neuro-imaging analysis under the expertise of Dr G
Venkatasubramanian
Now I want to pursue a career of a clinician scientist and
train myself in basic science I have been fortunate that Dr
Ravi Muddashetty has kindly agreed to train me at molecular
genetics laboratory at inStem NCBS under this fellowship
Currently I am also pursuing PhD in Psychiatry at NIMHANS
During this proposed research I wish to further elucidate the
biopsychosocial vulnerabilities for substance misuse in alcohol
naive children from multiplex alcohol-dependence families
using Imaging-genomics approach
The RTF has provided the right platform for a young
clinician like me I hope to continue with translational research
and clinical work as an independent investigator the field of
neuroimaging and psychiatric genetics with expertise in
alcoholism
Dr Bharat Holla NIMHANS Bangalore
3
Medicine was an automatic career choice for me as no
other profession can boast of doing social good while
challenging one academically and giving one a sense of
purpose The choice of specializing in pathology was
spontaneous for apart from providing answers to my curious
questions on the why‟s and how‟s of most diseases it is a
subject so full of color and at times so full of instant satisfaction
besides providing scope for teaching and research which I
wish to be very actively involved in
The research projects I have taken up so far (through
MBBS Internship and MD thesis) have given me a small glimpse
into the world of research and have motivated me enough to
want to pursue a research based approach in my practice of
Pathology With this background after completing my MD
studies joining St John‟s as Lecturer of Pathology in 2013 was
an instinctive decision for apart from the pleasant work
environment it nurtures budding researchers through many
inspiring clinicians like my principle supervisor Dr Usha Kini
Having worked with her team on the diagnostics aspects of
Hirschsprung disease over the past 2 years we are now
studying the molecular aspects of the disease Realising the
need to tie up with a molecular biologist I now work in Dr
Sudhir Krishna‟s lab at the National Institute of Biological
Sciences where I am learning the various molecular
principles and techniques to carry out the proposed
research
My pursuit to learn and implement molecular biology in
Medicine took me to the Molecular Medicine unit head at
St John‟s who told me that in order to fulfill my quest I need
3 things 1 an interest to learn molecular biology 2
adequate time to learn (1 hour per day after clinical work
would not suffice) and 3 the financial resource to access
these techniques As a pathologist my interest in molecular
biology stemmed from the calling to go beyond
morphological diagnosis to understanding the projections of
molecular alterations that drive disease into the realm of
morphology And although morphological diagnosis is
challenging in itself I wanted to use my two-dimensional
morphological view of disease as a gateway to understand
the three (and higher) dimensional molecular world of
disease much of which may appear difficult to interpret but
never the less is the need of the hour to provide
personalized therapies to our patients It was along this track
that I came across this India Alliance RTF which would not
only provide me the financial resource but above all the
protected time to learn and apply the various molecular
techniques while still retaining my feet in clinical medicine
Dr Maria Frances Bukelo St Johnrsquos Medical College Bangalore
Dr Sanjay K Chilbule Christian Medical College Vellore
After fellowship in paediatric orthopaedics at CMC
Vellore under supervision of Dr Vrisha Madhuri I joined one
of her research project to design the compliance monitored
clubfoot brace (Padma Pada) in collaboration with
engineers from IISc Bangalore It was quite inspiring to see
the replacement of age old brace by newer better and
comfortable brace which parents are not ready to let of
due to its definite advantage for child This was possible due
to Dr Vrisha‟s scientific disposition and the fact that clinician
themselves with the help of collaborators can bring in the
changes in the patient management adapting the research
in their prospectus
While working with Dr Vrisha‟s for cartilage and bone
regeneration involving human and animal experiments we
started to extend our thinking to one more field Outcome of
the osteosarcoma (OS) which is a commonest bone tumour
in children is not very favorable due to heterogeneity and
variable response to chemotherapy With availability of
patients and advanced laboratory in same unit we started
exploring this field initially with collaboration with
radiotherapy and medical oncology units at CMC Vellore In
literature we found out that most of the CSC research work
done for OS is being done on cell lines We started working
on cancer stem cells (CSCs) from osteosarcoma tissue from
patients with definite aim of translating this knowledge for
management of the osteosarcoma in future
In addition of learning all the bench work related to
planned work the Research Training Fellowship is providing
the unique opportunity to a clinician like me to be part of
basic science arena and to be able to develop a scientific
temperament This RTF is definitely metamorphosing the
thinking process to apply the basic science for the
orthopaedic disorders and to opt research as a career
continuing the clinical work
The Wellcome TrustDBT India Alliance
RESEARCH TRAINING FELLOWS
4
INDIA ALLIANCE
PUBLIC ENGAGEMENT CORNER
DNA70 Public Lecture Series
India Alliance organises several public lectures at various institutions across India to give those interested in science an opportunity to interact with eminent scientists from around the
world
In 1944 Oswald Avery together with Colin MacLeod and
Maclyn McCarty made the landmark discovery that
deoxyribonucleic acid (DNA) and not proteins carry genetic
information and is therefore the basis of inheritance In the 70
years since Avery‟s discovery DNA has come a long way
India Alliance celebrated the discovery of DNA as a
hereditary molecule through a series of public lectures in
various cities in 2014-15 given by researchers who have done
pioneering work centered around the DNA molecule The four
lectures in this series were given by Prof W Ian Lipkin (Center
for Infection and Immunity Mailman School of Public Health
Columbia University USA) and Prof Nadrian Seeman
(Margaret and Herman Sokol Professor of Chemistry New York
University USA) Dr Karen Nelson (President J Craig Venter
Institute Rockville USA) and Prof Shankar Balasubramanian
(University of Cambridge UK)
Our first speaker in this series Prof W Ian Lipkin a well-known
expert on the use of molecular methods for pathogen
discovery gave a lecture titled ldquoBad bugs on the big screen
science fiction and fact in Hollywoodrdquo in New Delhi discussed
how filmmakers often mix fact with fiction when dealing with
science stories whereas his second talk ldquoSmall Game Hunting
disease control in the genome erardquo in Bangalore provided a
comprehensive review of pathogen discovery microbiome
research and zoonotic diseases Our second speaker in this
series inventor of the field of DNA Nanotechnology Dr
Nadrian Seeman gave lectures in New Delhi Hyderabad
Kolkata and Shantiniketan where his talks on structural DNA
nanotechnology received very many questions from both
eager scientists and curious nonscientists The third lecture in
this series given by Dr Karen Nelson focused on the human
microbiome emerging infectious diseases and implications of
both for human health which was very aptly titled ldquoThe Zoo in
Yourdquo The last lecture in the DNA70 Public Lecture Series was
given by Prof Shankar Balasubramanian of University of
Cambridge co-inventor of next generation genome
sequencing technology and co-founder of the company
Solexa His lecture ldquoDecoding Human Genome on a
population scalerdquo discussed the history of DNA sequencing
the method that was developed by him and his colleagues at
Cambridge University for rapidly decoding genomes and the
impact of these technologies on life sciences medicine and
society For those of you who missed his lectures in Delhi and
Bangalore here‟s a short report
Report Prof Balasubramanian‟s lecture began with a humble
yet engaging account of his scientific beginnings in the
Department of Chemistry at University of Cambridge
followed by his successful association with another chemist Dr
David Klenerman along with whom he developed the
genome sequencing technology He described how
5
contributions of various scientists in elucidating the DNA
code- one of them being the father of genomics Fred
Sanger- influenced and shaped his work in this field He
recounted how they accidently invented this
technology as what they had really set out to study was
the motion of the DNA polymerase as it synthesised a
single DNA molecule using fluorescent tagging He
took the audience through the chemical processes of
DNA polymerisation and how his lab exploited these
processes to attach a fluorescent molecule on the
nucleic acid bases which enabled them to visualize the
different bases in a DNA molecule This chemistry was
then employed to develop the sequencing technology
which is now being commercialized by Illumina after it
acquired the company Solexa originally formed by Drs
Balasubramanian and Klenerman in 1998 During his talk
at IISc Bangalore Prof Balasubramanian admitted that
the practical question of how the information derived
from the Human Genome Project can be made useful
in comparing genomes from different individuals
inspired him to invent this quick method of DNA
sequencing Towards the end of the lecture Prof
Balasubramanian described a few incidents where his
method of sequencing had been useful for physicians to
perform diagnosis and develop personalised therapies
to treat patients
He acknowledged among others the support of the
UK funding body BBSRC for giving wings to their idea
when it was in its most naiumlve and nascent stage almost
20 years ago
Both the lectures were followed by an engaging
QampA session with an audience of more than 250 in
attendance at both venues which covered scientific
ethical sociological and commercial aspects of the
genome sequencing technology Some of the questions
raised at the session intended to discuss the impact of
genome sequencing on society genome of a
bdquoperfectly‟ healthy individual future of epigenome and
protein sequencing and possibility of reducing the cost
of the existing sequencing technologies for which Prof
Balasubramanian offered optimistic but practical
answers Apart from senior scientists the audience
mainly comprised of young students and researchers
who continued to interact enthusiastically with the
speaker well after the talk was over
Public Engagement Competition for India Alliance Fellows
To enable our Fellows to effectively and creatively engage with the
society about biomedical science we announced the first rolling bdquoPublic
Engagement competition‟ in May 2014 This competition is a valuable
opportunity for our Fellows to showcase and share their Science with the
Public and collaborate with other members of the society The
engagement can be through research social activities teaching arts
moviesdocumentary and other modes of knowledge sharing with the
central goal of educating and improving public awareness of science
and human health issues To apply please download the application
form here and send the completed application form to
publicengagementwellcomedbtorg
Image Competition for India Alliance Fellows
We are pleased to announce the launch of the Research Image
Competition for our Fellows where we invite you to submit images related
to biomedical research and healthcare Images could include
photographs clinical amp scientific images hand-drawn illustrations
Images must convey a scientific principle or a relevant human health
perspective Images can be produced by individuals or by a team
However the Fellow has to play a key role in the production of the
image Images can be submitted for both science and human health
categories but only two for each category will be allowed
Submitting the images Email your high-quality image with an easy-to-
understand description and a short image title to
publicengagementwellcomedbtorg Please mention the names of all
the people who were involved in producing the image
Deadline to submit images 15 October 2015
DNA70 Public Lecture Series
6
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Colorectal cancer (CRC) is the third most commonly
diagnosed cancer type approximately one million individuals
worldwide are diagnosed with the disease each year Anti-
epidermal growth factor receptor (EGFR) therapies such as
monoclonal antibody (cetuximab) against EGFR are either
administered as part of first-line treatment or as a final option
when other treatments fail However half of the CRC patients
who harbor mutations in KRAS NRAS and BRAF genes acquire
resistance to anti-EGFR drugs thus highlighting the necessity
for additional targeted therapies In the current study we
have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)
is highly expressed among CRC patients and demonstrated
the functional significance of SPINK1 in disease progression
and metastases SPINK1 over-expression in CRC has been
associated with advanced stage of the disease poor clinical
outcome and metastasis to liver
We have shown that silencing SPINK1 in BRAF mutation
positive WiDr colon adenocarcinoma cells demonstrate
decrease in cell proliferation invasion soft agar colony
formation and reduced tumor growth and distant metastases
in in-vivo model systems Importantly SPINK1 silencing led to
up-regulation of various metallothionein isoforms considered
as tumor suppressors in CRC which confers sensitivity to
chemotherapeutic drug doxorubicin Taken together our
findings strengthen the rationale for using the combinatorial
treatment approach for the SPINK1-positive CRC patients Our
study also demonstrates an important role for the SPINK1 over-
expression in CRC disease progression a phenomenon that
needs careful evaluation towards effective therapeutic target
development
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression R Tiwari S K Pandey S Goel V Bhatia S Shukla X Jing S M Dhanasekaran and B Ateeq Oncogenesis (2015)
Image SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin
Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins
expression DR BUSHRA ATEEQ Intermediate Fellow IIT Kanpur
Signal regulation at the mRNA 3rsquo-end Role of Phosphorylation Phosphorylation regulates gene specificity
DR RAKESH SINGH LAISHRAM Intermediate Fellow Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram
Gene expression in humans involves multiple steps from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP)
Poly(A) tail is essential for stability and efficient translation of
the mRNA Star-PAP is a non-canonical PAP that selects mRNA
target for polyadenylation Star-PAP together with co-
regulator PIPKIα controls expression of genes involved in
oxidative stress response and apoptosis We showed that
phosphorylation of Star-PAP determines specificity of its target
gene expressions downstream of signaling pathways
7
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
The Wellcome TrustDBT India Alliancersquos two-year Research Training Fellowship was launched in 2014 and is a first-of-its-kind
programme for clinicians in India This mentored programme is unique in terms of the expectations it has set out for the structure of the training programme and involvement it demands from the research supervisors The provision to get trained under the dual supervision of a clinical and a basic science researcher and the flexibility to attend coursesworkshops allows Clinicians and Allied Health professionals to receive systematic training in research methodology Some of the awarded Fellows from the first round of these Fellowships share their views on this Fellowship and how it will help them in the career paths they have chosen to pursue Click on their images to find out more about their current research projects
INDIA ALLIANCE
RESEARCH TRAINING FELLOWS Clinical and Public Health Research Fellowships
More information on the India Alliance Clinical
and Public Health Fellowships can be found at
httpwellcomedbtorgfellowshiptypeclinical-
and-public-health-research-fellowships
Aiming at a surgical career I was fortunate enough to
get into post-graduation in the subject of Oral and
Maxillofacial Surgery at one of the premier institutes in India
SDM college of Dental Sciences is the first institute in India to
have a dedicated Craniofacial Surgery unit performing over
1500 surgeries every year The patient problems included but
not restricted to oro-facial clefts trauma head and neck
oncology facial esthetic surgeries and infections Facial
trauma remains one of the most common procedures
performed by the maxillofacial surgeons Joining Mazumdar
Shaw Medical Center as a fellow in Cranio-Maxillofacial
Surgery provided me the necessary niche to take this
clinical problem to lab Mazumdar Shaw medical Center
sports a dedicated state-of-the-art research lab facility with
numerous research projects currently underway Professor
Dr Paul C Salins the Chief of Cranio-Maxillofacial Services
and Medical Director of the hospital encouraged me to
take up basic science research in this field Dr Aditya
Chaubey the Chief Scientific Officer of Mazumdar Shaw
Centre for Translational Research who has been working
extensively in the field of stem cells and has already
developed excellent in vivo models for bone regeneration
and scaffold designing accepted to guide me in starting a
research career I feel this research training fellowship will
allow me to dedicate my time in this exciting field and may
in fact allow me to pursue a translational research career in
the future Though inexperienced I believe that undertaking
this fellowship at an early stage of my career will help me in
better understanding of the existing clinical problems and
developing a scientific problem solving attitude and apply
the newly acquired skills in patient care
Dr Muralidhara Nagarjuna Mazumdar Shaw Center for
Translational Research
Bangalore
Training in the prestigious Bangalore Medical College and
Research Institute gave me a strong foundation in clinical
medicine I stood 1st for the state in the UG Medical Karnataka
Common Entrance Test Right from the early days of MBBS I
was fascinated by a career in a field that involves treatment
and research of neuropsychiatric disorders I consider myself
privileged to have obtained MD Psychiatry at NIMHANS which
is a premiere multidisciplinary academic research and health
care institute in Brain - Mind - Behaviour Axis in India I
developed a keen interest in addiction psychiatry and did my
MD thesis dissertation and also a post-doctoral addiction
psychiatry clinical fellowship under the guidance of Dr Vivek
Benegal During this time I also trained myself in advanced
neuro-imaging analysis under the expertise of Dr G
Venkatasubramanian
Now I want to pursue a career of a clinician scientist and
train myself in basic science I have been fortunate that Dr
Ravi Muddashetty has kindly agreed to train me at molecular
genetics laboratory at inStem NCBS under this fellowship
Currently I am also pursuing PhD in Psychiatry at NIMHANS
During this proposed research I wish to further elucidate the
biopsychosocial vulnerabilities for substance misuse in alcohol
naive children from multiplex alcohol-dependence families
using Imaging-genomics approach
The RTF has provided the right platform for a young
clinician like me I hope to continue with translational research
and clinical work as an independent investigator the field of
neuroimaging and psychiatric genetics with expertise in
alcoholism
Dr Bharat Holla NIMHANS Bangalore
3
Medicine was an automatic career choice for me as no
other profession can boast of doing social good while
challenging one academically and giving one a sense of
purpose The choice of specializing in pathology was
spontaneous for apart from providing answers to my curious
questions on the why‟s and how‟s of most diseases it is a
subject so full of color and at times so full of instant satisfaction
besides providing scope for teaching and research which I
wish to be very actively involved in
The research projects I have taken up so far (through
MBBS Internship and MD thesis) have given me a small glimpse
into the world of research and have motivated me enough to
want to pursue a research based approach in my practice of
Pathology With this background after completing my MD
studies joining St John‟s as Lecturer of Pathology in 2013 was
an instinctive decision for apart from the pleasant work
environment it nurtures budding researchers through many
inspiring clinicians like my principle supervisor Dr Usha Kini
Having worked with her team on the diagnostics aspects of
Hirschsprung disease over the past 2 years we are now
studying the molecular aspects of the disease Realising the
need to tie up with a molecular biologist I now work in Dr
Sudhir Krishna‟s lab at the National Institute of Biological
Sciences where I am learning the various molecular
principles and techniques to carry out the proposed
research
My pursuit to learn and implement molecular biology in
Medicine took me to the Molecular Medicine unit head at
St John‟s who told me that in order to fulfill my quest I need
3 things 1 an interest to learn molecular biology 2
adequate time to learn (1 hour per day after clinical work
would not suffice) and 3 the financial resource to access
these techniques As a pathologist my interest in molecular
biology stemmed from the calling to go beyond
morphological diagnosis to understanding the projections of
molecular alterations that drive disease into the realm of
morphology And although morphological diagnosis is
challenging in itself I wanted to use my two-dimensional
morphological view of disease as a gateway to understand
the three (and higher) dimensional molecular world of
disease much of which may appear difficult to interpret but
never the less is the need of the hour to provide
personalized therapies to our patients It was along this track
that I came across this India Alliance RTF which would not
only provide me the financial resource but above all the
protected time to learn and apply the various molecular
techniques while still retaining my feet in clinical medicine
Dr Maria Frances Bukelo St Johnrsquos Medical College Bangalore
Dr Sanjay K Chilbule Christian Medical College Vellore
After fellowship in paediatric orthopaedics at CMC
Vellore under supervision of Dr Vrisha Madhuri I joined one
of her research project to design the compliance monitored
clubfoot brace (Padma Pada) in collaboration with
engineers from IISc Bangalore It was quite inspiring to see
the replacement of age old brace by newer better and
comfortable brace which parents are not ready to let of
due to its definite advantage for child This was possible due
to Dr Vrisha‟s scientific disposition and the fact that clinician
themselves with the help of collaborators can bring in the
changes in the patient management adapting the research
in their prospectus
While working with Dr Vrisha‟s for cartilage and bone
regeneration involving human and animal experiments we
started to extend our thinking to one more field Outcome of
the osteosarcoma (OS) which is a commonest bone tumour
in children is not very favorable due to heterogeneity and
variable response to chemotherapy With availability of
patients and advanced laboratory in same unit we started
exploring this field initially with collaboration with
radiotherapy and medical oncology units at CMC Vellore In
literature we found out that most of the CSC research work
done for OS is being done on cell lines We started working
on cancer stem cells (CSCs) from osteosarcoma tissue from
patients with definite aim of translating this knowledge for
management of the osteosarcoma in future
In addition of learning all the bench work related to
planned work the Research Training Fellowship is providing
the unique opportunity to a clinician like me to be part of
basic science arena and to be able to develop a scientific
temperament This RTF is definitely metamorphosing the
thinking process to apply the basic science for the
orthopaedic disorders and to opt research as a career
continuing the clinical work
The Wellcome TrustDBT India Alliance
RESEARCH TRAINING FELLOWS
4
INDIA ALLIANCE
PUBLIC ENGAGEMENT CORNER
DNA70 Public Lecture Series
India Alliance organises several public lectures at various institutions across India to give those interested in science an opportunity to interact with eminent scientists from around the
world
In 1944 Oswald Avery together with Colin MacLeod and
Maclyn McCarty made the landmark discovery that
deoxyribonucleic acid (DNA) and not proteins carry genetic
information and is therefore the basis of inheritance In the 70
years since Avery‟s discovery DNA has come a long way
India Alliance celebrated the discovery of DNA as a
hereditary molecule through a series of public lectures in
various cities in 2014-15 given by researchers who have done
pioneering work centered around the DNA molecule The four
lectures in this series were given by Prof W Ian Lipkin (Center
for Infection and Immunity Mailman School of Public Health
Columbia University USA) and Prof Nadrian Seeman
(Margaret and Herman Sokol Professor of Chemistry New York
University USA) Dr Karen Nelson (President J Craig Venter
Institute Rockville USA) and Prof Shankar Balasubramanian
(University of Cambridge UK)
Our first speaker in this series Prof W Ian Lipkin a well-known
expert on the use of molecular methods for pathogen
discovery gave a lecture titled ldquoBad bugs on the big screen
science fiction and fact in Hollywoodrdquo in New Delhi discussed
how filmmakers often mix fact with fiction when dealing with
science stories whereas his second talk ldquoSmall Game Hunting
disease control in the genome erardquo in Bangalore provided a
comprehensive review of pathogen discovery microbiome
research and zoonotic diseases Our second speaker in this
series inventor of the field of DNA Nanotechnology Dr
Nadrian Seeman gave lectures in New Delhi Hyderabad
Kolkata and Shantiniketan where his talks on structural DNA
nanotechnology received very many questions from both
eager scientists and curious nonscientists The third lecture in
this series given by Dr Karen Nelson focused on the human
microbiome emerging infectious diseases and implications of
both for human health which was very aptly titled ldquoThe Zoo in
Yourdquo The last lecture in the DNA70 Public Lecture Series was
given by Prof Shankar Balasubramanian of University of
Cambridge co-inventor of next generation genome
sequencing technology and co-founder of the company
Solexa His lecture ldquoDecoding Human Genome on a
population scalerdquo discussed the history of DNA sequencing
the method that was developed by him and his colleagues at
Cambridge University for rapidly decoding genomes and the
impact of these technologies on life sciences medicine and
society For those of you who missed his lectures in Delhi and
Bangalore here‟s a short report
Report Prof Balasubramanian‟s lecture began with a humble
yet engaging account of his scientific beginnings in the
Department of Chemistry at University of Cambridge
followed by his successful association with another chemist Dr
David Klenerman along with whom he developed the
genome sequencing technology He described how
5
contributions of various scientists in elucidating the DNA
code- one of them being the father of genomics Fred
Sanger- influenced and shaped his work in this field He
recounted how they accidently invented this
technology as what they had really set out to study was
the motion of the DNA polymerase as it synthesised a
single DNA molecule using fluorescent tagging He
took the audience through the chemical processes of
DNA polymerisation and how his lab exploited these
processes to attach a fluorescent molecule on the
nucleic acid bases which enabled them to visualize the
different bases in a DNA molecule This chemistry was
then employed to develop the sequencing technology
which is now being commercialized by Illumina after it
acquired the company Solexa originally formed by Drs
Balasubramanian and Klenerman in 1998 During his talk
at IISc Bangalore Prof Balasubramanian admitted that
the practical question of how the information derived
from the Human Genome Project can be made useful
in comparing genomes from different individuals
inspired him to invent this quick method of DNA
sequencing Towards the end of the lecture Prof
Balasubramanian described a few incidents where his
method of sequencing had been useful for physicians to
perform diagnosis and develop personalised therapies
to treat patients
He acknowledged among others the support of the
UK funding body BBSRC for giving wings to their idea
when it was in its most naiumlve and nascent stage almost
20 years ago
Both the lectures were followed by an engaging
QampA session with an audience of more than 250 in
attendance at both venues which covered scientific
ethical sociological and commercial aspects of the
genome sequencing technology Some of the questions
raised at the session intended to discuss the impact of
genome sequencing on society genome of a
bdquoperfectly‟ healthy individual future of epigenome and
protein sequencing and possibility of reducing the cost
of the existing sequencing technologies for which Prof
Balasubramanian offered optimistic but practical
answers Apart from senior scientists the audience
mainly comprised of young students and researchers
who continued to interact enthusiastically with the
speaker well after the talk was over
Public Engagement Competition for India Alliance Fellows
To enable our Fellows to effectively and creatively engage with the
society about biomedical science we announced the first rolling bdquoPublic
Engagement competition‟ in May 2014 This competition is a valuable
opportunity for our Fellows to showcase and share their Science with the
Public and collaborate with other members of the society The
engagement can be through research social activities teaching arts
moviesdocumentary and other modes of knowledge sharing with the
central goal of educating and improving public awareness of science
and human health issues To apply please download the application
form here and send the completed application form to
publicengagementwellcomedbtorg
Image Competition for India Alliance Fellows
We are pleased to announce the launch of the Research Image
Competition for our Fellows where we invite you to submit images related
to biomedical research and healthcare Images could include
photographs clinical amp scientific images hand-drawn illustrations
Images must convey a scientific principle or a relevant human health
perspective Images can be produced by individuals or by a team
However the Fellow has to play a key role in the production of the
image Images can be submitted for both science and human health
categories but only two for each category will be allowed
Submitting the images Email your high-quality image with an easy-to-
understand description and a short image title to
publicengagementwellcomedbtorg Please mention the names of all
the people who were involved in producing the image
Deadline to submit images 15 October 2015
DNA70 Public Lecture Series
6
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Colorectal cancer (CRC) is the third most commonly
diagnosed cancer type approximately one million individuals
worldwide are diagnosed with the disease each year Anti-
epidermal growth factor receptor (EGFR) therapies such as
monoclonal antibody (cetuximab) against EGFR are either
administered as part of first-line treatment or as a final option
when other treatments fail However half of the CRC patients
who harbor mutations in KRAS NRAS and BRAF genes acquire
resistance to anti-EGFR drugs thus highlighting the necessity
for additional targeted therapies In the current study we
have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)
is highly expressed among CRC patients and demonstrated
the functional significance of SPINK1 in disease progression
and metastases SPINK1 over-expression in CRC has been
associated with advanced stage of the disease poor clinical
outcome and metastasis to liver
We have shown that silencing SPINK1 in BRAF mutation
positive WiDr colon adenocarcinoma cells demonstrate
decrease in cell proliferation invasion soft agar colony
formation and reduced tumor growth and distant metastases
in in-vivo model systems Importantly SPINK1 silencing led to
up-regulation of various metallothionein isoforms considered
as tumor suppressors in CRC which confers sensitivity to
chemotherapeutic drug doxorubicin Taken together our
findings strengthen the rationale for using the combinatorial
treatment approach for the SPINK1-positive CRC patients Our
study also demonstrates an important role for the SPINK1 over-
expression in CRC disease progression a phenomenon that
needs careful evaluation towards effective therapeutic target
development
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression R Tiwari S K Pandey S Goel V Bhatia S Shukla X Jing S M Dhanasekaran and B Ateeq Oncogenesis (2015)
Image SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin
Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins
expression DR BUSHRA ATEEQ Intermediate Fellow IIT Kanpur
Signal regulation at the mRNA 3rsquo-end Role of Phosphorylation Phosphorylation regulates gene specificity
DR RAKESH SINGH LAISHRAM Intermediate Fellow Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram
Gene expression in humans involves multiple steps from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP)
Poly(A) tail is essential for stability and efficient translation of
the mRNA Star-PAP is a non-canonical PAP that selects mRNA
target for polyadenylation Star-PAP together with co-
regulator PIPKIα controls expression of genes involved in
oxidative stress response and apoptosis We showed that
phosphorylation of Star-PAP determines specificity of its target
gene expressions downstream of signaling pathways
7
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
Medicine was an automatic career choice for me as no
other profession can boast of doing social good while
challenging one academically and giving one a sense of
purpose The choice of specializing in pathology was
spontaneous for apart from providing answers to my curious
questions on the why‟s and how‟s of most diseases it is a
subject so full of color and at times so full of instant satisfaction
besides providing scope for teaching and research which I
wish to be very actively involved in
The research projects I have taken up so far (through
MBBS Internship and MD thesis) have given me a small glimpse
into the world of research and have motivated me enough to
want to pursue a research based approach in my practice of
Pathology With this background after completing my MD
studies joining St John‟s as Lecturer of Pathology in 2013 was
an instinctive decision for apart from the pleasant work
environment it nurtures budding researchers through many
inspiring clinicians like my principle supervisor Dr Usha Kini
Having worked with her team on the diagnostics aspects of
Hirschsprung disease over the past 2 years we are now
studying the molecular aspects of the disease Realising the
need to tie up with a molecular biologist I now work in Dr
Sudhir Krishna‟s lab at the National Institute of Biological
Sciences where I am learning the various molecular
principles and techniques to carry out the proposed
research
My pursuit to learn and implement molecular biology in
Medicine took me to the Molecular Medicine unit head at
St John‟s who told me that in order to fulfill my quest I need
3 things 1 an interest to learn molecular biology 2
adequate time to learn (1 hour per day after clinical work
would not suffice) and 3 the financial resource to access
these techniques As a pathologist my interest in molecular
biology stemmed from the calling to go beyond
morphological diagnosis to understanding the projections of
molecular alterations that drive disease into the realm of
morphology And although morphological diagnosis is
challenging in itself I wanted to use my two-dimensional
morphological view of disease as a gateway to understand
the three (and higher) dimensional molecular world of
disease much of which may appear difficult to interpret but
never the less is the need of the hour to provide
personalized therapies to our patients It was along this track
that I came across this India Alliance RTF which would not
only provide me the financial resource but above all the
protected time to learn and apply the various molecular
techniques while still retaining my feet in clinical medicine
Dr Maria Frances Bukelo St Johnrsquos Medical College Bangalore
Dr Sanjay K Chilbule Christian Medical College Vellore
After fellowship in paediatric orthopaedics at CMC
Vellore under supervision of Dr Vrisha Madhuri I joined one
of her research project to design the compliance monitored
clubfoot brace (Padma Pada) in collaboration with
engineers from IISc Bangalore It was quite inspiring to see
the replacement of age old brace by newer better and
comfortable brace which parents are not ready to let of
due to its definite advantage for child This was possible due
to Dr Vrisha‟s scientific disposition and the fact that clinician
themselves with the help of collaborators can bring in the
changes in the patient management adapting the research
in their prospectus
While working with Dr Vrisha‟s for cartilage and bone
regeneration involving human and animal experiments we
started to extend our thinking to one more field Outcome of
the osteosarcoma (OS) which is a commonest bone tumour
in children is not very favorable due to heterogeneity and
variable response to chemotherapy With availability of
patients and advanced laboratory in same unit we started
exploring this field initially with collaboration with
radiotherapy and medical oncology units at CMC Vellore In
literature we found out that most of the CSC research work
done for OS is being done on cell lines We started working
on cancer stem cells (CSCs) from osteosarcoma tissue from
patients with definite aim of translating this knowledge for
management of the osteosarcoma in future
In addition of learning all the bench work related to
planned work the Research Training Fellowship is providing
the unique opportunity to a clinician like me to be part of
basic science arena and to be able to develop a scientific
temperament This RTF is definitely metamorphosing the
thinking process to apply the basic science for the
orthopaedic disorders and to opt research as a career
continuing the clinical work
The Wellcome TrustDBT India Alliance
RESEARCH TRAINING FELLOWS
4
INDIA ALLIANCE
PUBLIC ENGAGEMENT CORNER
DNA70 Public Lecture Series
India Alliance organises several public lectures at various institutions across India to give those interested in science an opportunity to interact with eminent scientists from around the
world
In 1944 Oswald Avery together with Colin MacLeod and
Maclyn McCarty made the landmark discovery that
deoxyribonucleic acid (DNA) and not proteins carry genetic
information and is therefore the basis of inheritance In the 70
years since Avery‟s discovery DNA has come a long way
India Alliance celebrated the discovery of DNA as a
hereditary molecule through a series of public lectures in
various cities in 2014-15 given by researchers who have done
pioneering work centered around the DNA molecule The four
lectures in this series were given by Prof W Ian Lipkin (Center
for Infection and Immunity Mailman School of Public Health
Columbia University USA) and Prof Nadrian Seeman
(Margaret and Herman Sokol Professor of Chemistry New York
University USA) Dr Karen Nelson (President J Craig Venter
Institute Rockville USA) and Prof Shankar Balasubramanian
(University of Cambridge UK)
Our first speaker in this series Prof W Ian Lipkin a well-known
expert on the use of molecular methods for pathogen
discovery gave a lecture titled ldquoBad bugs on the big screen
science fiction and fact in Hollywoodrdquo in New Delhi discussed
how filmmakers often mix fact with fiction when dealing with
science stories whereas his second talk ldquoSmall Game Hunting
disease control in the genome erardquo in Bangalore provided a
comprehensive review of pathogen discovery microbiome
research and zoonotic diseases Our second speaker in this
series inventor of the field of DNA Nanotechnology Dr
Nadrian Seeman gave lectures in New Delhi Hyderabad
Kolkata and Shantiniketan where his talks on structural DNA
nanotechnology received very many questions from both
eager scientists and curious nonscientists The third lecture in
this series given by Dr Karen Nelson focused on the human
microbiome emerging infectious diseases and implications of
both for human health which was very aptly titled ldquoThe Zoo in
Yourdquo The last lecture in the DNA70 Public Lecture Series was
given by Prof Shankar Balasubramanian of University of
Cambridge co-inventor of next generation genome
sequencing technology and co-founder of the company
Solexa His lecture ldquoDecoding Human Genome on a
population scalerdquo discussed the history of DNA sequencing
the method that was developed by him and his colleagues at
Cambridge University for rapidly decoding genomes and the
impact of these technologies on life sciences medicine and
society For those of you who missed his lectures in Delhi and
Bangalore here‟s a short report
Report Prof Balasubramanian‟s lecture began with a humble
yet engaging account of his scientific beginnings in the
Department of Chemistry at University of Cambridge
followed by his successful association with another chemist Dr
David Klenerman along with whom he developed the
genome sequencing technology He described how
5
contributions of various scientists in elucidating the DNA
code- one of them being the father of genomics Fred
Sanger- influenced and shaped his work in this field He
recounted how they accidently invented this
technology as what they had really set out to study was
the motion of the DNA polymerase as it synthesised a
single DNA molecule using fluorescent tagging He
took the audience through the chemical processes of
DNA polymerisation and how his lab exploited these
processes to attach a fluorescent molecule on the
nucleic acid bases which enabled them to visualize the
different bases in a DNA molecule This chemistry was
then employed to develop the sequencing technology
which is now being commercialized by Illumina after it
acquired the company Solexa originally formed by Drs
Balasubramanian and Klenerman in 1998 During his talk
at IISc Bangalore Prof Balasubramanian admitted that
the practical question of how the information derived
from the Human Genome Project can be made useful
in comparing genomes from different individuals
inspired him to invent this quick method of DNA
sequencing Towards the end of the lecture Prof
Balasubramanian described a few incidents where his
method of sequencing had been useful for physicians to
perform diagnosis and develop personalised therapies
to treat patients
He acknowledged among others the support of the
UK funding body BBSRC for giving wings to their idea
when it was in its most naiumlve and nascent stage almost
20 years ago
Both the lectures were followed by an engaging
QampA session with an audience of more than 250 in
attendance at both venues which covered scientific
ethical sociological and commercial aspects of the
genome sequencing technology Some of the questions
raised at the session intended to discuss the impact of
genome sequencing on society genome of a
bdquoperfectly‟ healthy individual future of epigenome and
protein sequencing and possibility of reducing the cost
of the existing sequencing technologies for which Prof
Balasubramanian offered optimistic but practical
answers Apart from senior scientists the audience
mainly comprised of young students and researchers
who continued to interact enthusiastically with the
speaker well after the talk was over
Public Engagement Competition for India Alliance Fellows
To enable our Fellows to effectively and creatively engage with the
society about biomedical science we announced the first rolling bdquoPublic
Engagement competition‟ in May 2014 This competition is a valuable
opportunity for our Fellows to showcase and share their Science with the
Public and collaborate with other members of the society The
engagement can be through research social activities teaching arts
moviesdocumentary and other modes of knowledge sharing with the
central goal of educating and improving public awareness of science
and human health issues To apply please download the application
form here and send the completed application form to
publicengagementwellcomedbtorg
Image Competition for India Alliance Fellows
We are pleased to announce the launch of the Research Image
Competition for our Fellows where we invite you to submit images related
to biomedical research and healthcare Images could include
photographs clinical amp scientific images hand-drawn illustrations
Images must convey a scientific principle or a relevant human health
perspective Images can be produced by individuals or by a team
However the Fellow has to play a key role in the production of the
image Images can be submitted for both science and human health
categories but only two for each category will be allowed
Submitting the images Email your high-quality image with an easy-to-
understand description and a short image title to
publicengagementwellcomedbtorg Please mention the names of all
the people who were involved in producing the image
Deadline to submit images 15 October 2015
DNA70 Public Lecture Series
6
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Colorectal cancer (CRC) is the third most commonly
diagnosed cancer type approximately one million individuals
worldwide are diagnosed with the disease each year Anti-
epidermal growth factor receptor (EGFR) therapies such as
monoclonal antibody (cetuximab) against EGFR are either
administered as part of first-line treatment or as a final option
when other treatments fail However half of the CRC patients
who harbor mutations in KRAS NRAS and BRAF genes acquire
resistance to anti-EGFR drugs thus highlighting the necessity
for additional targeted therapies In the current study we
have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)
is highly expressed among CRC patients and demonstrated
the functional significance of SPINK1 in disease progression
and metastases SPINK1 over-expression in CRC has been
associated with advanced stage of the disease poor clinical
outcome and metastasis to liver
We have shown that silencing SPINK1 in BRAF mutation
positive WiDr colon adenocarcinoma cells demonstrate
decrease in cell proliferation invasion soft agar colony
formation and reduced tumor growth and distant metastases
in in-vivo model systems Importantly SPINK1 silencing led to
up-regulation of various metallothionein isoforms considered
as tumor suppressors in CRC which confers sensitivity to
chemotherapeutic drug doxorubicin Taken together our
findings strengthen the rationale for using the combinatorial
treatment approach for the SPINK1-positive CRC patients Our
study also demonstrates an important role for the SPINK1 over-
expression in CRC disease progression a phenomenon that
needs careful evaluation towards effective therapeutic target
development
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression R Tiwari S K Pandey S Goel V Bhatia S Shukla X Jing S M Dhanasekaran and B Ateeq Oncogenesis (2015)
Image SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin
Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins
expression DR BUSHRA ATEEQ Intermediate Fellow IIT Kanpur
Signal regulation at the mRNA 3rsquo-end Role of Phosphorylation Phosphorylation regulates gene specificity
DR RAKESH SINGH LAISHRAM Intermediate Fellow Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram
Gene expression in humans involves multiple steps from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP)
Poly(A) tail is essential for stability and efficient translation of
the mRNA Star-PAP is a non-canonical PAP that selects mRNA
target for polyadenylation Star-PAP together with co-
regulator PIPKIα controls expression of genes involved in
oxidative stress response and apoptosis We showed that
phosphorylation of Star-PAP determines specificity of its target
gene expressions downstream of signaling pathways
7
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
INDIA ALLIANCE
PUBLIC ENGAGEMENT CORNER
DNA70 Public Lecture Series
India Alliance organises several public lectures at various institutions across India to give those interested in science an opportunity to interact with eminent scientists from around the
world
In 1944 Oswald Avery together with Colin MacLeod and
Maclyn McCarty made the landmark discovery that
deoxyribonucleic acid (DNA) and not proteins carry genetic
information and is therefore the basis of inheritance In the 70
years since Avery‟s discovery DNA has come a long way
India Alliance celebrated the discovery of DNA as a
hereditary molecule through a series of public lectures in
various cities in 2014-15 given by researchers who have done
pioneering work centered around the DNA molecule The four
lectures in this series were given by Prof W Ian Lipkin (Center
for Infection and Immunity Mailman School of Public Health
Columbia University USA) and Prof Nadrian Seeman
(Margaret and Herman Sokol Professor of Chemistry New York
University USA) Dr Karen Nelson (President J Craig Venter
Institute Rockville USA) and Prof Shankar Balasubramanian
(University of Cambridge UK)
Our first speaker in this series Prof W Ian Lipkin a well-known
expert on the use of molecular methods for pathogen
discovery gave a lecture titled ldquoBad bugs on the big screen
science fiction and fact in Hollywoodrdquo in New Delhi discussed
how filmmakers often mix fact with fiction when dealing with
science stories whereas his second talk ldquoSmall Game Hunting
disease control in the genome erardquo in Bangalore provided a
comprehensive review of pathogen discovery microbiome
research and zoonotic diseases Our second speaker in this
series inventor of the field of DNA Nanotechnology Dr
Nadrian Seeman gave lectures in New Delhi Hyderabad
Kolkata and Shantiniketan where his talks on structural DNA
nanotechnology received very many questions from both
eager scientists and curious nonscientists The third lecture in
this series given by Dr Karen Nelson focused on the human
microbiome emerging infectious diseases and implications of
both for human health which was very aptly titled ldquoThe Zoo in
Yourdquo The last lecture in the DNA70 Public Lecture Series was
given by Prof Shankar Balasubramanian of University of
Cambridge co-inventor of next generation genome
sequencing technology and co-founder of the company
Solexa His lecture ldquoDecoding Human Genome on a
population scalerdquo discussed the history of DNA sequencing
the method that was developed by him and his colleagues at
Cambridge University for rapidly decoding genomes and the
impact of these technologies on life sciences medicine and
society For those of you who missed his lectures in Delhi and
Bangalore here‟s a short report
Report Prof Balasubramanian‟s lecture began with a humble
yet engaging account of his scientific beginnings in the
Department of Chemistry at University of Cambridge
followed by his successful association with another chemist Dr
David Klenerman along with whom he developed the
genome sequencing technology He described how
5
contributions of various scientists in elucidating the DNA
code- one of them being the father of genomics Fred
Sanger- influenced and shaped his work in this field He
recounted how they accidently invented this
technology as what they had really set out to study was
the motion of the DNA polymerase as it synthesised a
single DNA molecule using fluorescent tagging He
took the audience through the chemical processes of
DNA polymerisation and how his lab exploited these
processes to attach a fluorescent molecule on the
nucleic acid bases which enabled them to visualize the
different bases in a DNA molecule This chemistry was
then employed to develop the sequencing technology
which is now being commercialized by Illumina after it
acquired the company Solexa originally formed by Drs
Balasubramanian and Klenerman in 1998 During his talk
at IISc Bangalore Prof Balasubramanian admitted that
the practical question of how the information derived
from the Human Genome Project can be made useful
in comparing genomes from different individuals
inspired him to invent this quick method of DNA
sequencing Towards the end of the lecture Prof
Balasubramanian described a few incidents where his
method of sequencing had been useful for physicians to
perform diagnosis and develop personalised therapies
to treat patients
He acknowledged among others the support of the
UK funding body BBSRC for giving wings to their idea
when it was in its most naiumlve and nascent stage almost
20 years ago
Both the lectures were followed by an engaging
QampA session with an audience of more than 250 in
attendance at both venues which covered scientific
ethical sociological and commercial aspects of the
genome sequencing technology Some of the questions
raised at the session intended to discuss the impact of
genome sequencing on society genome of a
bdquoperfectly‟ healthy individual future of epigenome and
protein sequencing and possibility of reducing the cost
of the existing sequencing technologies for which Prof
Balasubramanian offered optimistic but practical
answers Apart from senior scientists the audience
mainly comprised of young students and researchers
who continued to interact enthusiastically with the
speaker well after the talk was over
Public Engagement Competition for India Alliance Fellows
To enable our Fellows to effectively and creatively engage with the
society about biomedical science we announced the first rolling bdquoPublic
Engagement competition‟ in May 2014 This competition is a valuable
opportunity for our Fellows to showcase and share their Science with the
Public and collaborate with other members of the society The
engagement can be through research social activities teaching arts
moviesdocumentary and other modes of knowledge sharing with the
central goal of educating and improving public awareness of science
and human health issues To apply please download the application
form here and send the completed application form to
publicengagementwellcomedbtorg
Image Competition for India Alliance Fellows
We are pleased to announce the launch of the Research Image
Competition for our Fellows where we invite you to submit images related
to biomedical research and healthcare Images could include
photographs clinical amp scientific images hand-drawn illustrations
Images must convey a scientific principle or a relevant human health
perspective Images can be produced by individuals or by a team
However the Fellow has to play a key role in the production of the
image Images can be submitted for both science and human health
categories but only two for each category will be allowed
Submitting the images Email your high-quality image with an easy-to-
understand description and a short image title to
publicengagementwellcomedbtorg Please mention the names of all
the people who were involved in producing the image
Deadline to submit images 15 October 2015
DNA70 Public Lecture Series
6
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Colorectal cancer (CRC) is the third most commonly
diagnosed cancer type approximately one million individuals
worldwide are diagnosed with the disease each year Anti-
epidermal growth factor receptor (EGFR) therapies such as
monoclonal antibody (cetuximab) against EGFR are either
administered as part of first-line treatment or as a final option
when other treatments fail However half of the CRC patients
who harbor mutations in KRAS NRAS and BRAF genes acquire
resistance to anti-EGFR drugs thus highlighting the necessity
for additional targeted therapies In the current study we
have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)
is highly expressed among CRC patients and demonstrated
the functional significance of SPINK1 in disease progression
and metastases SPINK1 over-expression in CRC has been
associated with advanced stage of the disease poor clinical
outcome and metastasis to liver
We have shown that silencing SPINK1 in BRAF mutation
positive WiDr colon adenocarcinoma cells demonstrate
decrease in cell proliferation invasion soft agar colony
formation and reduced tumor growth and distant metastases
in in-vivo model systems Importantly SPINK1 silencing led to
up-regulation of various metallothionein isoforms considered
as tumor suppressors in CRC which confers sensitivity to
chemotherapeutic drug doxorubicin Taken together our
findings strengthen the rationale for using the combinatorial
treatment approach for the SPINK1-positive CRC patients Our
study also demonstrates an important role for the SPINK1 over-
expression in CRC disease progression a phenomenon that
needs careful evaluation towards effective therapeutic target
development
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression R Tiwari S K Pandey S Goel V Bhatia S Shukla X Jing S M Dhanasekaran and B Ateeq Oncogenesis (2015)
Image SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin
Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins
expression DR BUSHRA ATEEQ Intermediate Fellow IIT Kanpur
Signal regulation at the mRNA 3rsquo-end Role of Phosphorylation Phosphorylation regulates gene specificity
DR RAKESH SINGH LAISHRAM Intermediate Fellow Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram
Gene expression in humans involves multiple steps from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP)
Poly(A) tail is essential for stability and efficient translation of
the mRNA Star-PAP is a non-canonical PAP that selects mRNA
target for polyadenylation Star-PAP together with co-
regulator PIPKIα controls expression of genes involved in
oxidative stress response and apoptosis We showed that
phosphorylation of Star-PAP determines specificity of its target
gene expressions downstream of signaling pathways
7
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
contributions of various scientists in elucidating the DNA
code- one of them being the father of genomics Fred
Sanger- influenced and shaped his work in this field He
recounted how they accidently invented this
technology as what they had really set out to study was
the motion of the DNA polymerase as it synthesised a
single DNA molecule using fluorescent tagging He
took the audience through the chemical processes of
DNA polymerisation and how his lab exploited these
processes to attach a fluorescent molecule on the
nucleic acid bases which enabled them to visualize the
different bases in a DNA molecule This chemistry was
then employed to develop the sequencing technology
which is now being commercialized by Illumina after it
acquired the company Solexa originally formed by Drs
Balasubramanian and Klenerman in 1998 During his talk
at IISc Bangalore Prof Balasubramanian admitted that
the practical question of how the information derived
from the Human Genome Project can be made useful
in comparing genomes from different individuals
inspired him to invent this quick method of DNA
sequencing Towards the end of the lecture Prof
Balasubramanian described a few incidents where his
method of sequencing had been useful for physicians to
perform diagnosis and develop personalised therapies
to treat patients
He acknowledged among others the support of the
UK funding body BBSRC for giving wings to their idea
when it was in its most naiumlve and nascent stage almost
20 years ago
Both the lectures were followed by an engaging
QampA session with an audience of more than 250 in
attendance at both venues which covered scientific
ethical sociological and commercial aspects of the
genome sequencing technology Some of the questions
raised at the session intended to discuss the impact of
genome sequencing on society genome of a
bdquoperfectly‟ healthy individual future of epigenome and
protein sequencing and possibility of reducing the cost
of the existing sequencing technologies for which Prof
Balasubramanian offered optimistic but practical
answers Apart from senior scientists the audience
mainly comprised of young students and researchers
who continued to interact enthusiastically with the
speaker well after the talk was over
Public Engagement Competition for India Alliance Fellows
To enable our Fellows to effectively and creatively engage with the
society about biomedical science we announced the first rolling bdquoPublic
Engagement competition‟ in May 2014 This competition is a valuable
opportunity for our Fellows to showcase and share their Science with the
Public and collaborate with other members of the society The
engagement can be through research social activities teaching arts
moviesdocumentary and other modes of knowledge sharing with the
central goal of educating and improving public awareness of science
and human health issues To apply please download the application
form here and send the completed application form to
publicengagementwellcomedbtorg
Image Competition for India Alliance Fellows
We are pleased to announce the launch of the Research Image
Competition for our Fellows where we invite you to submit images related
to biomedical research and healthcare Images could include
photographs clinical amp scientific images hand-drawn illustrations
Images must convey a scientific principle or a relevant human health
perspective Images can be produced by individuals or by a team
However the Fellow has to play a key role in the production of the
image Images can be submitted for both science and human health
categories but only two for each category will be allowed
Submitting the images Email your high-quality image with an easy-to-
understand description and a short image title to
publicengagementwellcomedbtorg Please mention the names of all
the people who were involved in producing the image
Deadline to submit images 15 October 2015
DNA70 Public Lecture Series
6
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Colorectal cancer (CRC) is the third most commonly
diagnosed cancer type approximately one million individuals
worldwide are diagnosed with the disease each year Anti-
epidermal growth factor receptor (EGFR) therapies such as
monoclonal antibody (cetuximab) against EGFR are either
administered as part of first-line treatment or as a final option
when other treatments fail However half of the CRC patients
who harbor mutations in KRAS NRAS and BRAF genes acquire
resistance to anti-EGFR drugs thus highlighting the necessity
for additional targeted therapies In the current study we
have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)
is highly expressed among CRC patients and demonstrated
the functional significance of SPINK1 in disease progression
and metastases SPINK1 over-expression in CRC has been
associated with advanced stage of the disease poor clinical
outcome and metastasis to liver
We have shown that silencing SPINK1 in BRAF mutation
positive WiDr colon adenocarcinoma cells demonstrate
decrease in cell proliferation invasion soft agar colony
formation and reduced tumor growth and distant metastases
in in-vivo model systems Importantly SPINK1 silencing led to
up-regulation of various metallothionein isoforms considered
as tumor suppressors in CRC which confers sensitivity to
chemotherapeutic drug doxorubicin Taken together our
findings strengthen the rationale for using the combinatorial
treatment approach for the SPINK1-positive CRC patients Our
study also demonstrates an important role for the SPINK1 over-
expression in CRC disease progression a phenomenon that
needs careful evaluation towards effective therapeutic target
development
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression R Tiwari S K Pandey S Goel V Bhatia S Shukla X Jing S M Dhanasekaran and B Ateeq Oncogenesis (2015)
Image SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin
Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins
expression DR BUSHRA ATEEQ Intermediate Fellow IIT Kanpur
Signal regulation at the mRNA 3rsquo-end Role of Phosphorylation Phosphorylation regulates gene specificity
DR RAKESH SINGH LAISHRAM Intermediate Fellow Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram
Gene expression in humans involves multiple steps from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP)
Poly(A) tail is essential for stability and efficient translation of
the mRNA Star-PAP is a non-canonical PAP that selects mRNA
target for polyadenylation Star-PAP together with co-
regulator PIPKIα controls expression of genes involved in
oxidative stress response and apoptosis We showed that
phosphorylation of Star-PAP determines specificity of its target
gene expressions downstream of signaling pathways
7
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Colorectal cancer (CRC) is the third most commonly
diagnosed cancer type approximately one million individuals
worldwide are diagnosed with the disease each year Anti-
epidermal growth factor receptor (EGFR) therapies such as
monoclonal antibody (cetuximab) against EGFR are either
administered as part of first-line treatment or as a final option
when other treatments fail However half of the CRC patients
who harbor mutations in KRAS NRAS and BRAF genes acquire
resistance to anti-EGFR drugs thus highlighting the necessity
for additional targeted therapies In the current study we
have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)
is highly expressed among CRC patients and demonstrated
the functional significance of SPINK1 in disease progression
and metastases SPINK1 over-expression in CRC has been
associated with advanced stage of the disease poor clinical
outcome and metastasis to liver
We have shown that silencing SPINK1 in BRAF mutation
positive WiDr colon adenocarcinoma cells demonstrate
decrease in cell proliferation invasion soft agar colony
formation and reduced tumor growth and distant metastases
in in-vivo model systems Importantly SPINK1 silencing led to
up-regulation of various metallothionein isoforms considered
as tumor suppressors in CRC which confers sensitivity to
chemotherapeutic drug doxorubicin Taken together our
findings strengthen the rationale for using the combinatorial
treatment approach for the SPINK1-positive CRC patients Our
study also demonstrates an important role for the SPINK1 over-
expression in CRC disease progression a phenomenon that
needs careful evaluation towards effective therapeutic target
development
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression R Tiwari S K Pandey S Goel V Bhatia S Shukla X Jing S M Dhanasekaran and B Ateeq Oncogenesis (2015)
Image SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin
Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins
expression DR BUSHRA ATEEQ Intermediate Fellow IIT Kanpur
Signal regulation at the mRNA 3rsquo-end Role of Phosphorylation Phosphorylation regulates gene specificity
DR RAKESH SINGH LAISHRAM Intermediate Fellow Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram
Gene expression in humans involves multiple steps from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP)
Poly(A) tail is essential for stability and efficient translation of
the mRNA Star-PAP is a non-canonical PAP that selects mRNA
target for polyadenylation Star-PAP together with co-
regulator PIPKIα controls expression of genes involved in
oxidative stress response and apoptosis We showed that
phosphorylation of Star-PAP determines specificity of its target
gene expressions downstream of signaling pathways
7
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
This study reports an in vivo phosphorylation site on Star-PAP
at the N-terminus (serine 6 S-6) that determines Star-PAP
specificity for oxidative stress response genes The serine
kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus
that retains Star-PAP within the nucleus S6 phosphorylation is
required for the Star-PAP-PIPKIα interaction and mRNA
binding both critical for target mRNA selection However this
phosphorylation is indifferent to the expression of other target
genes (apoptotic genes) regulated by DNA damage via
other phosphorylation site(s) on Star-PAP This is a novel
mechanism where specificity of a poly(A) polymerase (or
even a polymerase) for its target gene expression is
determined by phosphorylation status This study also shows a
signal-mediated stimulation of CKIα kinase activity that
regulates distinct mRNA
Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity Mohan N Sudheesh AP Francis N Anderson R and Laishram RS 2015 Nucleic Acid Res (doi 1011093nargkv676)
A global regulatory switch that controls cellular development in bacteria
Sunish Kumar Radhakrishnan Intermediate Fellow IISER Thiruvananthapuram
The circular nature of bacterial chromosomes leads to the
formation of catenated (intermolecular linkage between two
replicated molecules of DNA) daughter chromosomes at the
end of each replication cycle These catenated
chromosomes need to be resolved by decatenation to
enable the proper segregation of the chromosomes into the
dividing daughter cells The decatenation function is primarily
carried out at the end of each replication cycle by one of
the DNA cutters type II topoisomerases in bacteria
topoisomerase IV (topo IV) which is also a quinolone
antibiotic target Interestingly the activity of topo IV has been
shown to be restricted to the late stages of the cell cycle
despite it being associated with the chromosome even during
the early stages The question as to how the decatenation
activity of the topo IV is regulated during the early stages of
the cell cycle has remained unanswered
Through a genetic screen we have identified Negative
switch for topo IV decatenation Activity (NstA) as a novel
negative regulator of the decatenation activity of topo IV
during early stages of the cell cycle in the dimorphic
bacterium Caulobacter crescentus A combination of DNA
replication S-phase specific synthesis and proteolysis ensures
that the presence of NstA is confined to the early stages of the
cell cycle Mechanistically we show that NstA exerts its
function by directly binding to topo IV and that the activity of
NstA is controlled by the oxidation state during the cell cycle
Investigating further we discovered for the first time a cyclical
fluctuation in the intracellular oxidation-reduction (redox)
state of bacterial cells Based on these evidences we have
proposed the dynamic intracellular redox state as a novel
global regulatory switch that controls cellular development
which might have major implications on the cell cycle control
of bacterial pathogens exposed to the chemical warfare of
the host immune system
A cell cycle-controlled redox switch regulates the topoisomerase IV activity Narayanan S Janakiraman B Kumar L and Radhakrishnan SK (2015) Genes amp Development
8
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
Human papilloma virus (HPV) accounts for the most
common cause of all virus-associated human cancers
However despite large-scale genome wide DNA sequencing
efforts of the cancer genome there is no dedicated
informatics tool to rapidly detect the presence of HPV in these
genomes in an exclusive manner In this study we present a
novel freely distributable computational tool ldquoHPVDetectorrdquo
(through a weblink download-- httpwwwactrecgovinpi-
webpagesAmitDuttHPVdetectorHPVDetectorhtml) to
detect all known HPV types along with their sites of integration
in the host genome using next generation sequencing data
set along with a widely compatible annotated reference of
143 HPV genome as a resource This user friendly tool has
been designed for researchers who has limited computational
expertise using graphical user interface (GUI) that requires
minimal third party tools Using HPVDetector one can analyze
paired end whole exome whole genome or whole
transcriptome dataset to detect all known HPV types along
with their sites of integration in the host genome The tool can
run in two modes a quick detect mode can identify co-
infection of HPVs and their quantitative abundance while
integration mode can identify HPV integration loci in human
genome and provide comprehensive HPV specific
annotations (Fig 1)
Based on our evaluation with 116 exome 23 transcriptome
and 1 whole genome HPVDetector was able to identify
presence of HPV in 20 exome and 4 transcriptome data
Using the annotation module we could show that viral gene
E7 was most widely represented among all the reads
detected that is a known viral oncogene Additionally the
integration module allowed us to validate known HPV
integration sites identify known fragile sites of the human
genome as HPV integration site and novel integration sites (Fig
2) In summary HPVDetector is a simple yet precise and robust
tool for detecting HPV from tumour samples using variety of
NGS platforms including whole genome whole exome and
transcriptome-- first tool of its kind solely dedicated to detect
the presence of HPV types from a diverse variety of NGS data
set
NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genomeP Chandrani V Kulkarni P Iyer P Upadhyay R Chaubal P Das R Mulherkar R Singh and A Dutt
A new and free computational tool for HPV detection DR AMIT DUTT Intermediate Fellow ACTREC Tata Memorial Centre Mumbai
Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector Site of integration as determined by HPVDetector in cervical cancer samples is shown HPV16 integration sites are depicted by circles and HPV18 by rectangles Black open and grey circles or rectangles represent integrations at known fragile sites at known integration sites and at novel sites respectively
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Conceptual The flowchart represents workflow for HPVDetector Paired-end reads obtained from next-generation sequencing data are aligned to a combined HumanndashHPV reference database All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module
9
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
Proteins regulating the formation of melanin-producing melanosomes DR SUBBA RAO GANGI SETTY Senior Fellow IISc Bangalore
Melanosomes are a class of lysosome-related organelles
(LROs) produced by specialised cells called melanocytes
which play a key role in skin color and photoprotection
against ionizing radiations Formation of this organelle requires
efficient and accurate transport of melanin synthesizing
enzymes from tubular or vesicular recycling membrane-bound
sacs called endosome to pre-mature melanosomes which
then undergo further maturation into fully pigmented
melanosomes This process is defective in Hermansky-Pudlak
syndrome patients due to the mutations in Biogenesis of LROs
Complexes (BLOC-1 -2 and -3) However the function of
these complexes in LRO biogenesis is only partially known In
the Journal of Cell Biology publication we have elucidated
the function of the three-subunit protein complex BLOC-2 in
relation to LRO biogenesis for the first time Our studies
demonstrate that BLOC-2 defines the specificity to the
melanosomal cargo containing recycling tubular endosomes
in targeting them to maturing melanosomes Furthermore
mutations in BLOC-2 mistarget the recycling endosomes to
multiple cell organelles such as plasma membrane
endosomes lysosomes Golgi and a subset to hypopigmented
melanosomes Moreover the SNARE proteins responsible for
mediating these membrane fusion events are unknown In the
Journal of Cell Science report we have provided the first clear
evidence that a recycling endosomal Soluble NSF (N-
ethylmaleimide-sensitive factor) Attachment Protein REceptor
(SNARE) protein regulates the cargo delivery and biogenesis
of pigment granules In addition our studies show that
mutations in a particular region of a SNARE protein STX13
increased its activity and redistributed it to melanosomes
indicating a role for that region in recycling the SNARE to
endosomes Our studies also found that another SNARE
protein VAMP7 localised to melanosomes controls the
trafficking of STX13 and its dependent transport steps Taken
together these studies show that BLOC-2 directs the recycling
of tubular endosomes to maturing melanosomes and STX13-
VAMP7 together mediate the membrane fusion between
these cell organelles
I STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis Jani RA Purushothaman LK Rani S Bergam P and Setty SR J Cell Sci July 2015
II BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery Dennis MK Mantegazza AR Snir OL Tenza D Acosta-Ruiz A Delevoye C Zoger R Sitaram A de Jesus-Rojas W Ravichandran K Rux J Sviderskaya EV Bennett DC Raposo G Marks MS and Setty SR J Cell Biol May 2015
Dr Settyrsquos research image on the cover of
Journal of Cell Science
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Please email your research stories and publications to
publicengagementwellcomedbtorg
10
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
Dr Urvakhsh Mehta is a clinician researcher and Wellcome TrustDBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute In this interview he tells us the impact of his current research how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated
INDIA ALLIANCE FELLOW IN SPOTLIGHT
DR URVAKHSH MEHTA Early Career Fellow NIMHANS Bangalore
What are you working on And what impact do you hope it will have
My research is focused on understanding schizophrenia
from a ldquosocial brain disorderrdquo perspective This stems from
important observations we have had in India that are
shared by colleagues from around the world that individuals
with schizophrenia have difficulties in perceiving processing
and responding to social cues in day to day interactions An
important neural-marker of these bdquosocial cognition‟ deficits in
schizophrenia is a dysfunctional ldquomirror neuron systemrdquo Mirror
neurons have a dual role of firing while one performs an
action as well as while one observes the same action This
unique property may provide the brain with a template to
understand intentions underlying observed actions and
hence may be relevant in processing social information In
my IA-funded research I am using a combination of
functional imaging and transcranial magnetic stimulation
(TMS) to understand plasticity of the mirror neuron system
and its role in supporting these complex social cognition
abilities in individuals with untreated schizophrenia
Results from this experiment will give us crucial information
regarding the connectivity of the mirror neuron system and its
relationship to social cognition in schizophrenia If transcranial
magnetic stimulation can adaptively modulate the mirror
neuron system this bdquoplasticity‟ can be further harnessed in
treating social cognition deficits using novel brain stimulation
techniques in future
What inspired you to become a clinician scientist
It has been a combination of factors that have inspired me
to choose the path of being a clinician scientist These range
from my upbringing and the freedom my parents gave me
to pursue my interests my long-standing curiosity with
cognitive neuroscience my training in psychiatry to the
excellent support and mentorship I have received from my
teachers and guides at NIMHANS The latter has actually
enabled me to pursue a single line of research over the last
8 years now Having trained in psychiatry and interacting
closely with individuals challenged with severe psychiatric
Urvakhsh with his current mentor Dr Jagadisha (Top) and with his
lsquogreat-grand mentor Dr MS Keshavan(below)
11
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
INDIA ALLIANCE FELLOW IN SPOTLIGHT
URVAKHSH MEHTA
disorders like schizophrenia and bipolar disorder provides us
with a unique vantage point to identify lacunae in our
understanding of these complex brain disorders from a
translational perspective I was introduced to the concept of
social cognition by a visiting professor ndash I continue to have a
very fruitful collaboration with him till date and he fondly
acknowledges me as his great-grand mentee I soon learnt
that this special cognitive ability had evolutionary salience in
humans ndash more so because of the well-documented co-
evolutionary association between brain size and social
complexity in several mammals Early in my training days this
ldquosocial brainrdquo framework to study schizophrenia excited me
as it provided an overarching conceptualization of
different symptom dimensions of this disorder ranging from
bizarre delusions and ego-boundary disturbances to avolition
and disorganized behavior I have since then studied the
clinical importance and neurobiology of these intriguing
cognitive abilities in patients with schizophrenia
How has Wellcome TrustDBT India Alliance funding helped you and your research
The India Alliance Fellowship could not have come at a
better time for me in my career It has certainly had a huge
impact First it was due to the IA-Fellowship that I could join
NIMHANS as a faculty in the department of psychiatry and
continue my line of research and clinical work in parallel
Second the financial grant through this Fellowship has helped
me start quite a complex experiment that is both technology
and manpower intensive The selection committee has been
sensitive to my needs and has made some really important
suggestions that I have been happy to implement Third this
Fellowship has given me an opportunity to train in novel
research applications of brain imaging and
neuronavigational TMS at Boston Both India Alliance and
NIMHANS have been supportive and permitted me to pursue
a PhD in psychiatry My training and experience over these
This image shows how target regions from functional MRI activation
maps superimposed on to the subjects structural brain image can be
precisely stimulated using infra-red camera guided TMS coil placement
Find out more about Urvakhsh‟s research here
four years will surely go a long way in shaping me as an
independent clinician scientist in India Lastly I have been
recruited as a regular faculty at NIMHANS (Assistant Professor of
Psychiatry) this year I am sure the recognition and the
opportunities provided by the IA-Fellowship have had a positive
impact on my selection process
What keeps you going everyday
This is something that is perhaps never a constant Over the
years I have learnt to draw inspiration and hope from wherever
I can ndash a sporting event a catchy song a new place I visit my
work and most importantly from people around me My family
friends teachers students colleagues and patients are always
there to give me so many ldquoahardquo moments that teach me
something new or generate ideas
Also music is something that keeps me going It is my default
mode ndash if I am not doing anything music is my constant ldquobrain
wormrdquo Anything from Shahid Parvez and Rashid Khan to Mark
Knopfler and Eagles can help me rewind
12
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH Senior Fellow
Since its discovery Acquired Immune Deficiency
Syndrome or AIDS has caused an estimated more than 36
million deaths worldwide Its causative agent the Human
Immunodeficiency Virus (HIV) has thus been an active topic
of basic and translational research India has the third largest
HIV epidemic in the world accounting for ~ 21 million infected
people Socio-economic conditions such as malnutrition
smoking alcohol drugs and poor hygiene are some of the
factors increasing the risk of HIV infection Despite the
availability of multiple anti-retroviral therapies against HIV the
disease remains a chronic life-long infection due to the ability
of virus to stay hidden within infected blood cells These
cellular ldquoreservoirsrdquo maintain HIV in a latent state where body‟s
immune response is unable to sense their presence and
current anti-HIV drugs show limited activity
The cellular reservoirs of latent HIV are found in diverse
anatomical locations including the genital tract bone
marrow brain lymphoid and the lymphoid tissue These
reservoirs persist even in the presence of Highly Active
Antiretroviral Therapy (HAART) today‟s standard of care
Understanding the fundamental basis of HIV-1 latency to
develop effective intervention strategies remains one of the
core research issues in the field Within this theme one
proposed eradication strategy is to activate these latently
infected cells followed by killing using HAART The
rationalisation for this kind of strategy can be two-fold First by
stimulating latently infected cells to reactivate the virus can
potentially lead to more rapid death of the infected cells due
to HIV replication Second once reactivated the cellular
reservoir producing HIV will be recognised by the immune
system Lastly simultaneous use of a reactivating agent along
with HAART can prevent subsequent spread of infection
However many of the research efforts in this direction yielded
no results due to generalised cytotoxicity associated with the
reactivating agents We believe that this is mainly due to lack
of basic tools to directly monitor the internal environment of
cells harboring virus in latent or reactivation state
In this context our research group is interested in
developing basic technologies to understand the physiology
of HIV infected cells during various stages of infection The
information generated from these methodologies can then be
exploited to develop high-throughput cellular screens (HTS) to
eradicate latent reservoirs of HIV Studies at both the cellular
and organismal levels revealed that HIV induces major
metabolic changes in the human host cells Some of these
changes include depletion of amino acids increased sugar
metabolism energy depletion and depolarised membrane
potential We found that in addition to metabolic changes
levels of reactive oxygen species and antioxidant glutathione
(GSH) are markedly influenced during HIV latency and
reactivation Healthy human cells produce oxygen free
radicals called reactive oxygen species (ROS) as a byproduct
of normal metabolism However various conditions including
chronic infection metabolic dysfunctions ageing and
prolonged chemotherapy can result in accumulation of these
ROS and generation of toxic levels of oxidative stress
Interestingly we discovered that heightened oxidative stress is
one of the primary causes of reactivation of HIV from the
latently infected cells Since GSH serves as a major cellular
antioxidant and functions as a protective shield against the
oxidative stress any changes in the cellular ROS levels directly
perturbs GSH balance Our team has devised a non-invasive
biosensor methodology new to the HIV field for precise
imaging and measurements of GSH levels within the sub-
compartments (eg mitochondria endoplasmic reticulum
and cytosol) of HIV infected cells Earlier methods use whole
cell or tissue extracts which destroy real-time information
related to the variations in GSH levels at a sub-cellular
resolution
13
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
FEATURE ARTICLE
PEEKING INTO THE HIV INFECTED CELLS
Eradicating HIV reservoirs by ldquoShock and Killrdquo strategy Cells latently infected with HIV can be
treated with small molecule redox modulators to decrease their antioxidant capacity This would
result in inactivation and elevated replication of HIV leading to HIV-induced cell death and
recognition of HIV infected cells by the immune system Simultaneous use of HAART can prevent
spread and transmission of new HIV particles to the neighbouring bystander cells
Using our novel biosensor technology we discovered that
latently infected cells have higher levels of GSH which may
facilitate the long term persistence of HIV In contrast active
replication of HIV rapidly depletes GSH levels We also
disclosed that a modest decrease in intracellular GSH levels
and associated increase in ROS levels are sufficient to
reactivate virus from latency without causing cytotoxicity
Our findings for the first time provide precise numerical
indicators of how much cellular physiology can be perturbed
to reactivate virus from the sleeping mode without eliciting
toxic side effects This may help researchers to adopt a
shock-and-kill approach in which virus could be reactivated
by redox modulating compounds and subsequently flushed
by current anti-HIV drugs The fluctuation of GSH levels
detected by our biosensor also helps to delineate cellular
pathways which control latent and active stages of infection
In addition to infection with HIV co-infection with another
human pathogen Mycobacterium tuberculosis (Mtb) the
causative agent of tuberculosis (TB) is adversely impacting
the HIV and TB control programmes worldwide Number of
people dying with HIV-TB coinfection is increasing at an
alarming rate Because of this
World Health organisation (WHO)
has recently recommended
collaboration between HIV and TB
control strategies Therefore we
believe that studying the basic
biology of Mtb and HIV in co-
infection models is poised to make
more beneficial impact than
studying these pathogens alone In
light of this we exploited our
biosensor technology and
discovered that certain bioactive
molecules (eg complex lipids)
produced by Mtb specifically
interacts with HIV infected cells and
disturb GSH balance to facilitate
HIV reactivation Since TB is the
major cause of HIV related deaths
our findings have major mechanistic and therapeutic
potential for both TB and AIDS
Dr Amit Singh is an assistant professor at Indian Institute of Science Bangalore and WTDBT India Alliance Intermediate Fellow (2009) Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection As also mentioned in this piece his research group has ldquodeveloped a
novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infectionrdquo
To find out more about his research visit his lab website
14
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
IN CONVERSATION WITH
Dr Ajit Varki
Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at University of California San Diego USA He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny Dr Varki was one of the speakers of the India Alliance Public Lecture Series ldquoEvolution of Human mindrdquo in 2014 and gave fascinating talk titled ldquoAdventures in Anthropogeny What makes us Humanrdquo in different cities across the country In this interview he very candidly takes us through his scientific journey the multidisciplinary research he is involved in and shares some great advice for aspiring researchers
What motivated you to become a scientist
For as long as I can recall in my childhood I wanted to
become a physician ndash to be involved in the care and healing
of the sick However I was very fortunate to gain admission
into a very special medical school Christian Medical College
Vellore In those days (as it is today) the medical education at
CMC includes exposure to scientific inquiry and research
During my time there I had the good fortune to interact with
many prominent physicianscientists as well as basic scientists
Still I first and foremost wanted to be a physician But I
gradually came to realize that while medicine has many
aspects that are still an art form- a major aspect has to do with
understanding the human body biology and science
Realizing at the time that there were very few opportunities in
India for a physician to continue doing serious science I
decided to migrate to the United States where this type of
combination was very common I was very fortunate to
eventually gain access to training at one of the best centers at
Washington University at St Louis Thus I was able to combine
my continued interest in medicine with its scientific aspects
particularly in hematology and cancer biology Initially I
wanted to pursue the then exciting new approach of bone
marrow transplantation but I decided that before I got into
this I should learn more about the surfaces of human blood
cells Reading more about this I came to realize that all other
cells in cell sin the body are covered with a dense
complicated coating of sugar chains that very few people
were studying Eventually my postdoctoral training working
with Stuart Kornfeld ended up with the discovery of a genetic
disease in a rare human disorder that had very little to do with
blood or cancer But I became completely immersed in the
science of understanding glycans This of course is the nature
of science you never know where it leads you
Could you briefly take us through your scientific journey and about your interest in the human evolution How does that tie in with your research in the field of Glycobiology
I decided to start my independent career combining
medicine with the study of the special class of sugars called
sialic acids Early in my stint as an assistant professor I
happened to see a patient being given a form horse serum for
the treatment of a disease called aplastic anemia Not
surprisingly she developed an allergic reaction to the horse
serum after a few treatments In reading the literature I was
very surprised to find that others had just reported the allergic
reaction was not against horse proteins but against horse sialic
acids At first this did not make any sense to me as sialic acids
are present in all mammals in horses as well as in humans
Eventually I realized there was one particular kind of sialic acid
present on horse serum glycoprotein that was completely
missing in humans It took me another ten years but I finally
discovered the first known genetic difference between
humans and chimpanzees (our closest living evolutionary
cousins) in a gene involved in modifying Sialic acid This in turn
led me to the field of anthropogeny or explaining the origin of
humans Thus as you can see science led me from medicine
to glycobiology then into anthropogeny and I now combine
all 3 disciplines in my scientific activities
If you were not a scientist you would be
Lead singer in a rock n roll band
15
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
IN CONVERSATION WITH
Dr Ajit Varki
What according to you are the challenges in your field of research
Both fields in which I work face similar challenges In the first
case (anthropogeny) there is certainly a lot of interest in the
field but the amount of available information is very limited In
the second case (Glycobiology) you have an even bigger
problem in that most scientists are only dimly aware of this
ldquodark matter of the biological universerdquo which affects every
cell and every biological process in the body In the end the
biggest challenge faced by anthropogeny is not only the
difficulty in gaining new information but also in the synthesis of
information across many different fields of human knowledge
In the case of glycobiology the same two problems apply
Added to that is the difficulty that most scientists poorly aware
of even the basic information But in both fields things are
changing More and more information is becoming available
and I am fortunate and excited to be involved this phase of
development
What is the best advice you have ever received
There is a tendency to assume that much of science consists of
thinking up experiments quickly getting results and moving
on Two pieces of advice stick in my mind from my mentors
Stuart Kornfeld taught me that the most important thing about
doing an experiment is the amount of time you spent thinking
about what you want to do why you want to do it how you
are going to go about it maximizing the chance of getting
well-controlled interpretable results This used to be the norm in
the early days when reagents and resources were precious
Nowadays there is an unfortunate tendency for young
scientists to do ldquoquick and dirtyrdquo experiments to ldquoget an ideardquo
of what might be happening before doing the real
experiment In fact such ldquoquick and dirtyrdquo experiments waste
a huge amount of time and resources and one is often
back to square one In relation to doing experiments the other
important piece of advice I got was from a famous scientist
named Ray Lemieux a chemist in Canada Ray pointed out
to me that the great majority of experiments that we do are
ones in which we already sort of know what kind of result to
expect As Ray put it ldquoif you do an experiment and you get an
expected result you have not done an experimentrdquo In other
words experiments are often too predictable and those are
the kind we tend to do more often Another interesting
corollary is the most interesting outcome of an experiment is a
completely unexpected result As the famous science writer
Isaac Asimov put it The most exciting phrase to hear in
science the one that heralds new discoveries is not ldquoEurekardquo
but ldquoThats funnyrdquo Too often these days I find that young
people will do experiments and not getting the expected
result they become disappointed abandon their line of
reasoning and often do not even inform their advisors about
what they found thinking somehow that they have failed
Actually the time to get most excited is when the experiment
does not work out the way you thought even though you
designed it well and had all the right controls
Your message for young students and researchers
The pursuit of science (and the associated issues like winning
grants and getting papers accepted) can be sometimes slow-
going and frustrating and one usually lives for that occasional
day when the big breakthrough occurs But in the long run it is
hard to think of the most satisfying profession (other than that
of a successful rock n roll singer or orchestra conductor) Most
of my classmates who went through medicine and did not
pursue a scientific career are now bored with their professions
and trying to retire I wake up every morning and I cannot wait
to get to work
To find out more about Dr Varki‟s research visit his lab website
Dr Varki at Bangalore Science Forum
Dr Varki after his lecture at Indian Association for the Cultivation of
Science Kolkata with IA Grants Adviser Dr Ranjana Sarma IA Fellow
Dr Benu Brata Das (L-R)
16
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
Early Career Fellows DR MEGHA amp
DR NEHA VYAS
Early Career Fellows
For an academic research career in the life sciences
conventionally a highly productive postdoctoral stint is
considered necessary To meet this benchmark of productivity
as well as to hone their research skills the de facto route an
India-trained PhD student takes is to do a postdoc overseas
Other factors such as better salaries higher standard of living
and exposure to cutting-edge research also motivate this
migration Additionally the advice that overseas postdoctoral
research credentials are preferred for a faculty job in India
plays a significant role in this decision Reality underscores this
advice a majority of junior faculty hired in top Indian research
institutions have returned from a postdoc overseas Further
testament to the popularity of this status quo is that both DST
and DBT have Fellowships exclusively for those returning from
abroad
Shaking up this paradigm are researchers who choose to
pursue a postdoctoral career in India This option has gained
traction due to the increasing availability of institutions
laboratories and funding opportunities At the leading edge of
enabling this is the Early Career (EC) Fellowship scheme which
has done much to attract a cohort of ambitious postdocs to
research in India These Fellowships are generously funded
empowering Fellows to dream big set up and visit
international collaborations and tackle fundamental science
questions for a length of time that allows for rigorous pursuit
The EC Fellowships thus provide a great opportunity for a
fantastic early career start But this prompts an obvious follow-
up question what is the professional future of the EC Fellows
The mandate of the EC Fellowships is to support ideas that can
act as a springboard to the Fellow‟s future independent
research program This suggests the expectation that Fellows
would continue to pursue an academic research career
Given the lopsided supply and demand situation not just in
India but world over it should not be surprising that not all EC
Fellows would be successful in getting academic jobs Even
after taking this into account Fellows wishing to pursue this
professional path are struggling their interactions with the
Indian scientific community as prospective faculty applicants
reveal a dominant perception that EC Fellows should be
comparable to those who complete their postdoc overseas Is
this perception justified This article attempts to provide the EC
Fellow perspective and with the questions raised hopes to
start a conversation in the Indian scientific community about
the future of postdocs in India
The key yardstick used to assess scientific performance is
publication record Are the India Alliance and Indian faculty
screening committees expecting EC Fellows to deliver a
record similar to a postdoc in the West From the Fellows‟
point of view this is an apples-to-oranges comparison The EC
Fellow is working on an independent research idea right from
the start of their Fellowship while a conventional postdoc
typically works on ongoing projects in the Supervisor‟s
laboratory which may later morph into an independent
research project This research independence of the EC
Fellow though comes at a cost Experimental systems and
logistics have to be standardised and sometimes procured
and set up In some cases the Fellowship Supervisor‟s research
and the Fellow‟s project have little overlap and this further
exacerbates the time lag experienced to get publishable
results Another way to enhance research output is to build
collaborations within the laboratory and outside The EC
scheme allows for the latter but the former is completely
missing from the Indian laboratory landscape more than one
postdoc in an Indian lab is a rarity Even with international
collaboration the EC Fellows are working on their ideas and
not on the collaborators‟ ideas further reducing the chances
of the work in the collaborators‟ laboratory being
independently published These circumstances affect the
output that EC Fellows can have by the end of their tenure
and argues that EC Fellows may not have track records similar
to those doing a conventional postdoc in the West
OPINION ARTICLE
17
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
These parameters should not get masked in the shadow of the
sole currency of the current evaluation system ie ldquoimpact
factor of publication(s)rdquo
In the West a postdoctoral culture has existed for more than
30 years and postdocs are considered a major indispensible
work force in research This has resulted in a system for nurturing
postdocs and helping them transition to future careers
academic or otherwise A similar research environment is yet to
evolve in India simply because there was never a sizeable
cohort of postdocs But now since both funding agencies and
institutions are building postdoc cohorts a framework to foster
postdocs needs to be developed Managing a PhD is very
different from managing a postdoc and timely strategic
advice especially if the postdoc is interested in an academic
career will be valuable Skill development opportunities and
career planning resources for postdocs in Indian institutions
Post-doc India
International
Future Impact Factor Independent Research
Productivity
Early Career
policy
Indian Science
Scientific Community Fellowships
Academic
Funding Collaborations
First EC Fellows‟ publication record can be benchmarked
against the limitations inherent to doing research in India To
do this Indian institutions can reflect on the publication
record of their own junior faculty in the first five years of
having set up their independent laboratory
Second the quasi-independence of the EC Fellow in
terms of research idea execution and future vision can be
acknowledged
Third new scientific directions created by the Fellows in
their Fellowship Supervisor‟s laboratory can be considered
Fourth the ability to innovate and deliver on projects
independently in an Indian research environment should be
valued The EC Fellowship experience provides the Fellows
with an opportunity to develop a realistic idea of what can
be achieved in India and how
would only be possible if the community recognises this
cohort To this end the NCBS-inStem campus postdocs have
formed a postdoctoral association which aims to assist
postdocs in developing themselves professionally through
teaching and other career-related activities A postdoc-
specific symposium is being planned to make postdocs
visible as a research cohort within the Indian scientific
community Although geographically restricted at present
the formal recognition of the association at the policy level
and its implementation in institutions would be helpful
To conclude the following questions require reflection by
the Indian scientific community policy makers and the India
Alliance is India ready to host a postdoctoral culture Are
the issues raised here of publication record and postdoc
mentorship important to the development of postdoctoral
culture in our country As a community should we
encourage postdoc-ing in India If yes are there sufficient
opportunities and mechanisms to enable India-trained
postdocs to successfully transition into a career of their
choice A brain-storming session on the points raised here
would be useful not just for the future of EC Fellows but all
postdocs in India
Post-docing Vision
If the India Alliance and the Indian scientific community
intend to encourage postdoc-ing in India a more nuanced
assessment of Fellows performance might be considered
Training Cutting-edge Output Culture Publications Junior faculty
Transition
Supervisor Opportunities
Authors of this piece Drs Megha (ECF 2013) and Neha Vyas
(ECF 2010) are India Alliance‟s Early Career Fellows based at
National Centre for Biological Sciences and inStem
Bangalore respectively
Disclaimer The opinions expressed within this article are the personal
opinions of the author(s) The information facts or opinions appearing in
the article do not reflect the views of the India Alliance
Neha Vyas Megha
Alliance
DBT
Postdoctoral association
18
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
Leadership and management two sides of the same coin DR SHITAL SARAH AHALEY Early Career Fellow
ldquoThere is a difference between leadership and management Leadership is of the spirit compounded of personality and vision its practice is an art Management is of the mind a matter of accurate calculation its practice is a science Managers are necessary leaders are essentialrsquorsquo Field Marshal Lord Slim
In the academic world we are trained to hold a pipette design an experiment write reports and papers formulate and test a hypothesis and yet when we establish a lab we are expected to manage the lab funds and graduate students lead a group and achieve goals I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab We have to be
leaders and managers we have to practise the art of leadership and the science of management
In academia many learn management skills as and when they progress in their career The skills are acquired through experience There are times when one is successful at a task and other times where one fails One formula does not fit all situations or one type of training exercise does not apply to all graduate students Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances Others discuss with colleagues who may or may not have faced similar situations Yet there are some who are confident enough to handle situations without any help In any case one has to arrive at a decision the consequences good or bad have to be faced by the group leaderPI With trial and error the PI finally sets up a lab working ethics managerial techniques lab environment and eventually a leadership style The PI is definitely
managing a lab but may or may not be a good leader C J Fitzsimons the Leadership Sculptor who undertakes Laboratory Management course for EMBO defines leadership as bdquothe art of maintaining a dynamic balance between influencing others by word and deed to reach common goals and ensuring their development and well-beingrsquo
The EMBO management training for postdocs and group leaders addresses important skills including staff selection leadership and delegation effective problem solving and communication I attended the training for post-docs in May at Leimen Germany with C J Fitzsimons and Sabine Gramm as our guides If put in one sentence the skills that were addressed are the ones we are already aware of to some extent but the trainers put them as tangible formulas or theorems before us For example in ldquoMaking the Right Movesrdquo Edward O‟Neil provides us with an equation
Leadership = Vision + Relationships + Tasks
We all have an understanding of leadership and some ideas about how a good leader should be but this simple equation gives us a concrete perception of the term Additionally each term of this equation viz vision relationships and tasks were further spelled out to improve our understanding
Briefly the course covered the following topics such as impact of cultural differences leadership profile and skills PIgroup leader role impact of working environment working with values communication feedback and criticism team dynamics conflict management motivation delegation interview preparation We spent approximately 60 minutes on each of these topics Some topics like PIGroup leader role
required 120 minutes Each of the topics was elaborated based on extensive research done in the field by experts There were 17 participants of different nationalities- all of us were post-docs in different countries yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions One thing I realised significantly during this workshop was the lack of post-doc culture in India
The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork While we all possess certain leadership qualities this course helps us to identify and work on our qualities based on our personality type and circumstances All PIs have to run a lab and they do so to the best of their capability This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab
Prof Katja Schmitz a participant of the course from Clemens Schoumlpf Institute puts it aptly
ldquoIf yoursquore only interested in acquiring a few tools read a book or visit a seminar If yoursquod like to find out more about yourself and how that impacts your leadership get a coachrdquo
For further information visit wwwleadershipsculptorcom and wwwemboorgeventslaboratory-management-courses
Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research Pune Find out more about her here
REPORT
19
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
Dr Dipanwita Sengupta is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser Since then Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation In this interview she takes us through her childhood days her interest in music finding inspiration in prominent Bengali figures and more
What is your background
My family is quite multicultural with my mother who hails from
North West Frontier Province and my father from Lahore During
partition both my parent‟s families migrated to India and
made Delhi their new home Atmosphere at home was that of
discipline however it gave us freedom to explore the cultures
and traditions of both the families The best part of this was the
variety of food that my sister and I were exposed to I fondly
remember how as kids we used to wait the whole year for our
Dussehra holidays when we got the chance to visit our
maternal grandparents Every vegetable at their place was
grown in the small kitchen garden that my grandfather
maintained in the backyard ndash from tomatoes to bhindi (lady
finger) from mangoes to pomegranates ndash all these were
grown in-house After a whole day of mischief we used to get
dressed up in sweaters to go watch Ramlila at the colony park
ndash something which we don‟t see in the city anymore
Being in Delhi was an added advantage when it came to my
education the city being host to the best of schools colleges
and renowned universities in the country Even though I belong
to a family of engineers there was no pressure on us from our
parents to follow this family tradition I completed my studies
right from the schooling to PhD here in Delhi My first Postdoc
was at CNIC Madrid where I started a project on aging and
oxidative stress Economic crisis there took me to Pierre
Sonveaux‟s newly established group in Brussels where I worked
on tumor metabolism for 3 years In 2012 I decided to move
back to India and joined the Alliance as a grants adviser
How has your India Alliance journey been so far
Apart from working with an excellent team at the Alliance I
get to be in touch with the best minds in research Also it gives
me an opportunity to meet young PhD students and postdocs
through Scicomm workshops Their infectious energy and
questions drives me to keep myself updated with latest trends
in science Another good thing about our organization is its
capacity to evolve with time and situation without stagnation
When not busy on the job what do you enjoy doing
With the birth of my twin daughters last year my personal
interests have taken a back seat When not in office I am busy
attending to the whims and fancies of my little angels My
reading habit has changed gears from history and thrillers to
parenting books and articles I have a good collection of old
Hindi songs and ghazals which I think (and I hope) my
daughters like listening too
Who inspires you (living or dead)
Actually two people First being my Nanaji paternal
grandfather He was a self-made man During partition he
came to India barefoot with his family Without any aid he
rose from extreme paucity to becoming a very successful
businessman I never saw him relaxing he worked till the very
end He was a freedom fighter philanthropist and a strong
believer in girl education
The second is the renowned astronaut late Kalpana Chawla
From an ordinary girl born in Haryana to the first Indian-born
woman in space She fought for her dreams and realized them
too A quote from her last email - The path from dreams to
success does exist May you have the vision to find it the
courage to get on to it and the perseverance to follow it
inspires many Interestingly I share my birthday with her
INDIA ALLIANCE STAFF CORNER
DR SUVEERA DHUP Grants Adviser
Dr Suveera Dhup is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser Suveera has been involved with many aspects of IA from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme In this interview she takes us through her family history reminisces about her childhood days her love for ghazals people who inspire her and more
20
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
EXTERNAL EVENTS
9 travel awards were made to PhD students Postdocs and Young Investigators to cover travel expenses for this meeting
These were announced on 1 August 2015 The list below is the final list of Travel Awardees (excludes those who could not accept the award) The list is according to the Submission Number and not according to priority
The following will receive travel support of up to euro 500 each 1528 Uzma Saqib IIT Indore 1533 Mirza Saqib Baig IIT Indore 1540 Swarnendra Singh NII New Delhi 1572 Abhinita Borah IIT Bombay
India Alliance Travel Awards
Datetime 31 October - 0900 to 2 Nov 2015 - 1715
Event location The George Institute for Global Health New Delhi India
Clinical Research Training 2015
This training course has been developed to provide an overview of research study design and methods to young
researchers who have just completed their clinical training or are in the early stages of a research career The primary aim of the course is to provide knowledge with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project and taking the output to the next step ie publication For more information on this workshop and how to apply visit the website
1588 Manika Kargeti IIT Bombay 1591 Yasir Khan Aligarh Muslim University 1598 Alok Pandey CIMAP Lucknow 1623 Arun Prakash Mishra CCMB Hyderabad 1632 Thangaselvam Muthusamy NCBS Bangalore
Click on the image to find out more about YIM2016
21
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22
Please send your feedback suggestions and contributions to publicengagementwellcomedbtorg
Follow us on
IMAGES IN THIS ISSUE
Cover image (original) by Dr Subba Rao Gangi Setty Senior
Fellow IISc Bangalore
Image description Bright-field and immunofluorescence
microscopy image of wild-type mouse melanocytes expressing
mutated STX13 (a recycling endosomal Qa-SNARE) which results in
its mislocalisation to melanosomes Green mutant STX13 red a
melanosome-resident protein TYR black dots melanosomes
captured with bright-field microscopy
Credit R Dourmashkin Wellcome
Images
HIV particlesHuman immunodeficieny
virus (HIV-1) particles showing the core
and the envelope
Transmission electron micrograph
Collection Wellcome Images
Credit Dr Ajit Varki From Cell Reports
Nidoviruses attached to sialic acid (in
blue hemagglutinin esterase)
22