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Indo-US Science and Technology Forum Combating Cancer Indo-U.S. Collaborations Volume 11 (1) | May 2019 Indo-U.S. Science & Technology Forum Newsletter of IUSSTF

Newsletter of IUSSTF Volume 11 (1) | May 2019 · in India but has been limited by subjective observer variability. Despite the development of effective HPV vaccines, over 200,000

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Page 1: Newsletter of IUSSTF Volume 11 (1) | May 2019 · in India but has been limited by subjective observer variability. Despite the development of effective HPV vaccines, over 200,000

Indo-US Science and Technology Forum

Combating CancerIndo-U.S. Collaborations

Volume 11 (1) | May 2019

Indo-U.S. Science & Technology Forum

Newsletter of IUSSTF

Page 2: Newsletter of IUSSTF Volume 11 (1) | May 2019 · in India but has been limited by subjective observer variability. Despite the development of effective HPV vaccines, over 200,000

Editor-in-ChiefRajiv Kumar Tayal

Executive Director, IUSSTF

EditorNishritha Bopana

Principal Science Officer, IUSSTF

Associate Editor Pushpa Iyer

Program Officer, IUSSTF

Editorial Consultant Manoj Dabas

Layout Design / DTP Pramod Jha

Design, Production and CirculationCreative Edge Media and Services Pvt. Ltd. Aravali House, 431/D-22, Chhatarpur Hills

New Delhi-110074, India

CONTENTSCOVER STORY

Joint Center for Reducing Cancer Mortality through Cancer PreventionCombating Cancer

04Low-cost Companion Diagnostic Test for Predicting Benefit of Adjuvant Chemotherapy in ER+ Breast CancerTargetting Tumors

08

11 Multiplex biomarker assay for detection of all forms of Mycobacterium tuberculosis

12Diagnosing TB

IUSSTF Governing Board Meeting

24Events Diary

IUSSTF Joint Center On Proteomics Student Speak14Biomarkers for Wellness Giving Wings to Talent

17

Initiative for Research and Innovation in Science Young Turks

22

OpinionsOpinions expressed in Connect do not necessarily reflect the opinion of IUSSTF or other organizations associated

with publication of Connect.

Comments and SuggestionsPlease email the Connect Team at

[email protected]

Published and Printed byIndo-U.S. S&T Forum, Fulbright House, 12 Hailey Road

New Delhi - 110 001

Cover Photo : Breast cancer awareness and Abdominal cancer awareness, INDIA Source: iStock

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According to the World Health Organization, the global cancer burden is estimated to have risen to 18.1 million new cases and 9.6 million deaths in 2018. Combating this increasing burden cannot be accomplished in isolation. Collaboration – both national and international, not only brings together diverse minds to work on problems that affect us all, but also facilitates the development of a diverse, globally-engaged science and engineering workforce. These collaborations, however, cost money and very few mechanisms exist that allow for physical connectivity between different groups of researchers across countries. This is the precise gap that the Indo-U.S. Science & Technology Forum’s grant-in-aid support to facilitate scientific networks, attempts to fill. IUSSTF helps forge partnerships and supports medium-term engagements (2-3 years) through the Indo-U.S. Virtual Networked Joint Center Program aimed at addressing challenging problems in new and emerging frontline areas of science and technology. The United-India Science & Technology Endowment Fund (USISTEF) Program administered by IUSSTF is another unique Grant-in-Aid program to translate S&T innovation-driven ideas into market opportunities. This edition of Connect covers two projects – one each under these two initiatives - that are exploring ways to reduce Cancer mortality.

IUSSTF remains committed to nurture contacts between young students from India and the United States. With that in mind, 25 bright, young school students have been selected to participate in the Intel® International Science and Engineering Fair to be held in Phoenix later this month.

This past quarter we also held the IUSSTF Governing Board meeting, which is briefly covered in this edition as well. This meeting while helping us put our accomplishments in perspective; also provided the opportunity for us to brainstorm with our Governing Board members and explore avenues to reinvent both our programs and ourselves to meet the growing aspirations of our stakeholders!

From the Editor-in-Chief

Rajiv Kumar TayalExecutive Director, IUSSTF

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Cover Story

Joint Center for Reducing Cancer Mortality through Cancer Prevention

Combating Cancer

Basic biomedical research is providing knowledge of the carcinogenesis process at the molecular level, facilitating the identification of new screening biomarkers, risk assessment tools,

and targets for preventive interventions. However, translation of basic research to the benefit of individuals and populations at risk has not kept pace with discovery. Large countries such as India provide investigators access to populations with unique genetics and environmental exposures to identify and compare risk factors across populations for development of malignancies. They also present important challenges to population-based cancer risk-reduction—the need for low-cost, highly effective screening/early detection technologies, and portability to rural regions in resource limited settings.

The IUSSTF supported Joint Center for Reducing Cancer Mortality through Cancer Prevention, brings together scientists devoted to preventing cervical, breast and gallbladder cancers from the University of Michigan and Arizona State University in the U.S. and from All India Institute of Medical Sciences (AIIMS) and Amity University in India. The Joint Center employs 3 different approaches that model

Recent reductions in mortality from cancer in the developed world can be ascribed to simple, cost-effective, population-based screening (for example, stool/blood testing, visual examination of the oral cavity and cervix) supplemented by more expensive technology driven tests, such as mammography and human papilloma molecular viral testing for early diagnosis and effective treatment. This step-wise approach to preventing cancer needs improvement to exploit rapidly developing technologies that can not only reduce the costs to expand the reach of prevention to all, but also be more efficient.

Dean E. Brenner*, Max S. Wicha*, Patrick Schloss*, Justin Colacino*, Karen Anderson$, Mack T. Ruffin^*University of Michigan; $Arizona State University; ^ Pennsylvania State University

USA

Pramod Garg*, Neerja Bhatla*, Sujata Mohanty*, Anurag Srivastava*, Lalit Dar*, B.C. Das#

*All India Institute of Medical Sciences, New Delhi; #Amity Institute of Molecular Medicine & Stem Cell Research, NoidaINDIA

Figure 1: Breast cancer prevention teams from the University of Michigan and AIIMS working together at the AIIMS-DBT-Center of Excellence for Stem Cell Research in New Delhi

4 | Connect - May 2019

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the translational carcinogenesis continuum — clinically relevant, long-term, primary 3 dimensional (3D) human tissue culture models for mechanism discovery and therapeutic application; host-environment factors in carcinogenesis progression that will lead us to new diagnostic and preventive therapeutic strategies; and, clinical biomarker validation for detection of early stage neoplastic or pre-neoplastic lesions—all considered critical components of a well-rounded strategy in cancer prevention.

Reducing Breast Cancer MortalityBreast cancer is the highest incident cancer of women in India and in the U.S. Ductal carcinoma in situ (DCIS) is a precursor lesion to invasive breast cancer. The widespread implementation of mammography screening has resulted in a dramatic increase in the diagnosis of DCIS. Women with DCIS have a 2 to 10-fold increased risk of invasive cancer. DCIS and invasive lesions in the same patient have similar molecular signatures, suggesting they have the same neoplastic cell origin.

The Joint Center team has worked with a portfolio of natural products (turmeric extracts, resveratrol, ginger, omega-3 fatty acids, and broccoli extracts) that exploit Ayurvedic sources in contemporary scientific models. The team is targeting the neoplastic stem cell in DCIS as a strategy to select optimal interventions aimed at preventing the progression of DCIS to invasive lesion—the cancer.

To test whether such commonly used products have

true preventive effect, the Joint Center team recognized that cell lines and inbred rodent models that historically are useful to interrogate mechanisms, fail to model the diversity of human biology. They cannot be used to assess or predict therapeutic efficacy. The team has developed a 3D Matrigel-based culture system that can sustain prolonged growth (>1 yr) of primary human colonic tissue (normal, adenomas, adenocarcinomas) and recently with normal human breast tissue.

The AIIMS breast surgery resects 2 to 4 large (≥5 cm) breast masses weekly of which 10% are likely to be DCIS only without invasion. These tissue samples are sufficient to permit pathology evaluation and tissue for 3D culture. Over the summer and fall of 2018, AIIMS investigators (Dr. Sujata Mohanty and Ms. Sonali Rawat) visited the stem cell team at the University of Michigan. In December, 2018, reciprocal visits from the Michigan team worked together with the AIIMS team at the AIIMS-DBT-Center of Excellence for Stem Cell Research (Figure 1). Figure 2A depicts the graphical representation of overall research strategy under this joint platform. Figure 2B shows cells and early stage breast organoids isolated from DCIS lesions at AIIMS and developed by the Joint Team. Figure 2C shows examples of breast organoids grown at Michigan. A library of long term, 3D organoid cultures of normal human breast, ductal carcinoma in situ (DCIS), and invasive breast carcinoma epithelial

Newsletter of IUSSTFIndo-U.S.Virtual Networked Center

Figure 2 : Panels B and C: Three dimensional term organoid cultures of primary human breast tissues. Panel B is a three dimensional organoid growing from a human ductal carcinoma in situ (DCIS) at AIIMS, New Delhi. Panel C is an organoid growing from a normal human breast at the University of Michigan in Ann Arbor, Michigan, USA.

Figure 2 : Panel A: Graphical representation of overall research strategy under this joint platform

Breast Cancer Tumor sample 2D Culture 3D Culture

cancer genomes drug effect patient cells

Characterization

Patient Specific Treatment Options

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cells being jointly created by the AIIMS and Michigan team can be used to select optimal interventions such as customized nutraceuticals/herbal/Ayurvedic products for individual cancer prevention (“precision prevention”). This inexpensive strategy promises to reduce mortality from breast cancer.

Reducing Cervical Cancer MortalityHuman papilloma virus (HPV) causes cervical cancer, anogenital cancers, and a subset of oropharyngeal cancers, with over 250,000 deaths per year globally. Cervical cancer screening with cytology (“Pap”) smears and HPV DNA detection are not readily available in underserved populations in low and middle income countries due to cost and logistics. Visual inspection of the cervix with acetic acid (VIA) has reduced mortality in India but has been limited by subjective observer variability. Despite the development of effective HPV vaccines, over 200,000 new cases and over 100,000 deaths due to cervical cancer are estimated by 2020 in India accounting for 25% of the global burden of cases.

The Arizona State University Team has created a point-of-care device using miniaturized optical components of an automated ELISA assay into a simple and low-cost focal plane configuration. Green light emitting diodes (LEDs) and photodiodes eliminate the need for magnifying optics by sandwiching the fluorescent biorecognition layer directly between the LED emitter and photodiode in a face-to-face (focal plane) configuration. The current device (Figure 3) automates 16 ELISA assays on a single chip enabling detection of up to 14 different proteins with sensitivity to 10 pg.

This point-of-care device will be used to test for HPV antibodies as an inexpensive cervical cancer screening tool. Initial blood samples collected at AIIMS under the supervision of Dr. Neerja Bhatla and the OB-GYN oncology team at AIIMS are being used to test the new device and accompanying microarray technology in the AIIMS Virology Laboratory of Dr. Lalit Dar. Exchange visits between the Arizona State University, University of Michigan, and AIIMS groups have produced preliminary experimental data for the function of the device, standardization of laboratory and clinical protocols, and

a functional web-based database for data collection and sharing. The AIIMS team has studied and collected samples from 116 patients to date. Once validated, the new automated ELISA assay system will be tested in 13,000 women undergoing VIA in New Delhi and the surrounding rural villages. This low-cost device is likely to make screening for cervical cancer cost-effective and efficient for women in India by improving the reliability of current screening procedures and selecting only those women who need more complex care for further diagnosis and treatment.l

Cover Story

Figure 3 : Panel B: Schematic diagram of the LED detection technology enabling a small sized point of care device to perform highly sensitive immunoassays on a chip.

Figure 3 : Panel A: New point of care lateral flow microchip device capable of detecting up to 16 proteins on site without the need for a laboratory facility

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Cover Story

Breast cancer presently accounts for nearly 145,000 new cases in India annually as compared to 115,000 only about a decade ago. This dramatic, almost 30% increase

in breast cancer incidence, has led to an increased demand for predictive and prognostic companion diagnostic (CDx) assays to ascertain the aggressiveness of cancer phenotypes so that patients with less aggressive biology can be spared chemotherapy. Predictive CDx assays can also aid in design of clinical trials, and help reduce health care costs by optimizing treatment regimens. Most CDx tests in the United States and Europe are based on gene expression assays; however, this technology is beyond the reach of most of the population in India due to the high cost, limited resources, and need for specialized facilities. Additionally, these assays involve destructive testing of tissue; tissue being a valuable resource.

The goal of this U.S.-India Science & Technology Endowment Fund (USISTEF) project where Case Western Reserve University and Inspirata Inc. in the United States work in close collaboration with Tata Memorial Hospital in India, is to validate an accurate and

Vani ParmarTata Memorial Centre

Mumbai, INDIA

Anant MadabhushiCase Western Reserve

University, Cleveland, USA

Breast cancer acounts for the majority of cancers diagnosed amongst women in India with nearly 145,000 new cases in India annually. Under this USISTEF project the goal is to validate an accurate and low-cost prognostic test for identifying aggressive estrogen receptor positive (ER+) breast cancers, specific to the Indian population.

Low-cost Companion Diagnostic Test for Predicting Benefit of Adjuvant Chemotherapy in ER+ Breast Cancer

Targetting TumoRs

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low-cost prognostic test for identifying aggressive estrogen receptor positive (ER+) breast cancers, specific to the Indian population. This is because an overwhelming (about 80%) of cancers are ER+. Computerized image analysis of digitized images of routinely-acquired hematoxylin and eosin (H&E) stained slides of biopsy or surgical specimens with outcome data will yield a continuous image-based risk score (IbRiS) of cancer aggressiveness.

Current clinical guidelines for ER+ breast cancer recommend a course of chemotherapy in addition to hormone therapy, but most patients (who typically have

less aggressive disease) do not require chemotherapy. A gene-expression based test, Oncotype Dx, is available for treatment guidance in the U.S., but a low-cost alternative is necessary to serve the patient population in India. The increasing use and adoption of telepathology and availability of whole slide scanning technology has allowed for bridging the clinical care gap between urban and rural medical centers in India and also set the stage for the IbRiS based prognostic test in India. IbRiS will have several advantages over molecular assays such as ODx in that it (1) can interrogate the entire expanse of the pathology image enabling a more accurate capture of tumor heterogeneity and hence disease risk, (2) is non-disruptive of pathology workflow, (3) will be substantially cheaper, (4) non-destructive of tissue, and (5) faster.

Through this project we want to validate and commercialize a low cost computerized histologic image based risk score predictor (IbRiS) for identifying which early stage ER+ breast cancer patients will benefit from adjuvant chemotherapy. Through a comprehensive image based interrogation of disease morphology from digitized hematoxylin & eosin (H&E) stained slides, IbRiS will yield a continuous risk score; low IbRiS suggesting hormonal therapy is sufficient while adjuvant chemotherapy is

U.S.-India S & T Endowment Fund (USISTEF)

HER2+15%-20%

ER+65%-75%

All Breast Cancers

Triple negative 15%

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Cover Story

required for high IbRiS scores. While the visual reading of H&E slides by a pathologist is still remarkably useful for tumor characterization, sophisticated histomorphometric analysis with computer-aided image analysis has the potential to “unlock” more revealing sub-visual attributes about tumors just from morphology.

Recent advances in whole-slide scanning technology have made it possible to obtain and analyze large, high-resolution images of digitized histology. Histomorphometric image analysis can enable a detailed spatial interrogation (e.g. capturing nuclear orientation, texture, shape, architecture) of the entire tumor morphologic landscape and its most invasive elements from a standard H&E slide. Additionally, these sub-visual or “histologic biomarkers” can be correlated with disease recurrence independent of other clinical and pathologic features. The IbRiS classifier will take advantage of the expanding digital telepathology infrastructure across clinical centers in India to bring precision medicine prediction in a low resource setting. In order to train the IbRiS classifier among Indian women, we aim to create a digital histologic database of ER+ patients in India which will be vital due to differences in genotypic and phenotypic presentation of breast cancer between populations.

In a nutshell, the process involves first digitally scanning a regular H&E stained tissue slide obtained from a surgically resected specimen of ER+ breast cancer in women treated at TMH. Once the slide is scanned IbRiS goes through the entire slide and checks for the quality of the slide using several pre-determined parameters (amount of tissue, presence of artifacts). After the quality check, IbRiS makes use of proprietary, in-house computerized algorithms that automatically detects nuclei in the entire digitized

tissue image. Once that is accomplished, the tumor nuclei is segmented out and several subtle histomorphometric features relating to the shape, size, number, architecture and patterns of the nuclei are extracted out of each image. These features are used to build the final IbRiS classifier that can discriminate between ER+ breast with better survival than those with more aggressive phenotypes, based on clinical outcome data. Once developed IbRiS will be able to give the pathologist and the oncologist alike from a digitized H&E slide of a resected specimen, the apparent risk of aggressiveness based on a single click along with IbRiS feature maps individualized for each patient.

The project will converge expertise in computational imaging, surgery, and pathology in the U.S. and India, including from the Madabhushi group at Case Western Reserve University and Tata Memorial Hospital (TMH) in Mumbai; TMH is the largest tertiary cancer hospital in Asia. The U.S. team has developed and tested this technology on a number of cancer sites (head and neck, prostate, breast), but this project will focus specifically on Indian women diagnosed with early-stage, ER+ breast cancer. The industrial partner Inspirata Inc., a digital pathology based cancer diagnostics company, which has recently licensed a number of histomorphometry based technologies from the Madabhushi group and recently engaged Philips Digital Pathology in a Joint Development agreement, will help create the commercial prototype of IbRiS.

In less than six months since we began this project, we have been working on installing a whole slide scanner to digitize the tissue slides of breast cancer patients from Tata Memorial Hospital under the directions of Head of Pathology, Dr. Sangeeta Desai and Dr. Vani Parmar from the Dept. of Oncology. At the same time, we have also been implementing new histomorphometric features in the IbRiS model where we have recently shown that features related to the orientation of collagen fibres in the tumor adjacent stromal region are prognostic of disease free survival in ER+ breast cancer. In addition, we have also shown that a prototype of IbRiS developed on a large clinical trial in USA involving ER+ breast cancer (ECOG 2197) improved the Oncotype Dx classification of low-risk cases who did not suffer any recurrence by over 20% as compared to Oncotype Dx alone which in the real world translates to 20% more women who would do well without chemotherapy thus saving them the deleterious effects and expenses associated with chemotherapy.l

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The Nineteenth Meeting of the Governing Board (GB) of the Indo-U.S. Science and Technology Forum (IUSSTF) was held in New Delhi on 12th March 2019 under the Co-Chairmanship of Prof. Indranil Manna, JC Bose Fellow and Institute Chair Professor, Department of Metallurgical and

Materials Engineering, Indian Institute of Technology-Kharagpur (Acting Indian Co-Chair) and Dr. Jonathan Margolis, Deputy Assistant Secretary, Bureau of Oceans and International Environmental and Scientific Affairs, U.S. Department of State (U.S. Co-Chair).l

IUSSTF Governing Board Meeting

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Feature

Multiplex biomarker assay for detection of all forms of Mycobacterium tuberculosis

Diagnosing TBImran Khan*

*University of California, Davis School of Medicine, Sacramento, CA USA

Sarman Singh*, Puneet Kumar Gupta$, Vivek Chandra$

*All India Institute of Medical Sciences, Bhopal; $NextGen Invitro Diagnostics Pvt. Ltd., GurugramINDIA

To quote the World Health Organization’s Global Tuberculosis Report 2018, “worldwide, Tuberculosis (TB) is one of the top 10 causes of death and the leading

cause from a single infectious agent (above HIV/AIDS). Millions of people continue to fall sick with TB each year. In 2017, TB caused an estimated 1.3 million deaths among HIV-negative

people and there were an additional 300,000 deaths from TB among HIV-positive people. Globally, the best estimate is that 10.0 million people developed TB disease in 2017 and two thirds were in eight countries: India (27%), China (9%), Indonesia (8%), the Philippines (6%), Pakistan (5%), Nigeria (4%), Bangladesh (4%) and South Africa (3%)”.

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U.S.-India S & T Endowment Fund (USISTEF)

India ranks at the top among the tuberculosis endemic countries because TB case detection is inadequate and there are no good diagnostics available for pulmonary, extra-pulmonary and pediatric TB. High TB burden adversely affects social and economic conditions as well. TB is generally curable if diagnosed correctly and treated in a timely manner but the major weaknesses in India are inadequate diagnostic services and higher incidence with an increased potential for drug resistance.

This project funded by the U.S.-India Science and Technology Endowment Fund (USISTEF) Program proposes the development of a multiplex blood-based

test (RU-1) for the detection of all forms of TB. The test can be used on dried blood spots (that ensures easy collection in remote areas as well); displays 91% - 96% specificity; is instrument agnostic and runs on multiple systems including Point-of-Care. RU-1 has high throughput (upto 360 patients/day) and with automation, it can analyze thousands of samples per day. It is suitable for high-burden settings and provides quick turnaround of results when patient loads are high. These are major advancements over the current front line, WHO recommended, sputum smear (SS) AFB-microscopy test with low sensitivity (~50%) and throughput.l

OR

Figure 2: The Testing protocol for RU-1

Reconstituted 90 patientsamplesper plate

6 wells forcontrols

Multiplex M.tb. Antigens + Beads

M.tb. antibody

Incubate 1.5 hours

1 µlPlasma/serum

Vacuum filter/Wash2-3 Minutes

Add conjugatedsecondary antibody

Incubate 30 minutes

Vacuum filter/Wash2-3 minutes

Read plate onMAGPIX

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Feature

The Indo-U.S. Virtual Networked Functional and Computational Proteomics Research Center brings together novel capabilities and integrates innovative technologies in workflows to provide new diagnostic tools and tackle unmet disease areas in India.

IUSSTF Joint Center On Proteomics

BiomarkerS FOR Wellness

Functional proteomics has emerged as one of the key technologies in biomedical research aimed at developing a better understanding of disease

pathology and diagnostic cure. The Joint Center Team have come together with a goal to employ functional and computational proteomics to understand and unveil several broad biological questions pertaining to cancer and infectious diseases. Functional proteomics coupled with computational tools now enables a better understanding of signaling pathways, novel biomarker discovery and characterization of molecular targets to novel drug molecules.

IIT Bombay, ISB National Centre for Cell Science, Pune and the Biodesign Institute at Arizona State University, USA, together combine four complementary areas of research, forming an interdisciplinary team to achieve the following goals:

1. Conduct functional proteomics analysis such as protein microarrays and Surface Plasmon Resonance imaging for elucidation and validation of cellular pathways involved in breast cancer through protein interaction studies.

2. Develop and evaluate selected reaction monitoring assays for validation of Cancer and Tuberculosis biomarkers through mass spectrometry.

3. Perform computational simulations for the derived proteomics data for peptide identification and validation, quantification and data interpretation.

4. To explore the possibility of analyzing individualized omics profiles, and work towards an Indian Centric Wellness Project thorough personalized prevention and treatment.

5. To train the next generation of Indian scientists in the interdisciplinary and collaborative arena of proteomics.

Cancer Research Under the aegis of the Joint Center, Prof. Srivastava and his group travelled to the United States and during the visit, the group was able to optimize and develop Selected Reaction Monitoring (SRM) assays for screening candidate proteins with roles in Breast Cancer and Tuberculosis.

Sanjeeva SrivastavaIndian Institute of Technology

Bombay, INDIA

Robert MoritzInstitute for System Biology

Washington, USA

Srikanth RapoleNational Centre for Cell Sciences

Pune, INDIA

Joshua LaBaerThe Biodesign Institute at

Arizona State University, USA

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Indo-U.S. Virtual Networked Center

For the Breast Cancer project, the data available from literature on breast cancers was curated manually. This exercise led to a list of ~50 proteins with roles in different stages of the disease. These proteins were then searched against the Human plasma proteins (Human PlasmaAtlas at ISB) to arrive at a concise list with proteins present in human plasma. The new list was then searched against the Human breast peptides list to identify the peptides from breast related proteins. Once this list was finalized, all the reported transitions from the complete human SRMAtlas were exported. Data was then acquired against all the transitions and analyzed.

Tuberculosis ResearchTuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (MTB), is the leading cause of death due to infectious disease. Presently, one-third of the world’s population is infected with TB and each year new infections occur in about 1% of the population. In 2016, there were more than 10 million cases of active TB which resulted in 1.3 million deaths including more than 95% of deaths in developing countries, among which India, China, Indonesia, Pakistan, and the Philippines contributed to more than 50% of infection. MTB test- the gold standard for diagnostics, although sensitive and specific, is time-consuming and not routinely used in countries with a high prevalence of tuberculosis. Several other diagnostic methods including tuberculin skin tests, serological tests, and Rapid Diagnostic Tests (RDT) are employed but each has their own limitations. Thus a cheap, accurate, and rapid diagnostic test for tuberculosis will have an immense impact to check TB. Proteomic fingerprinting is an up-coming diagnostic concept based on the idea that disease states are somehow associated with distinctive configurations of circulating proteins. Because the biological complexity of most diseases means that individual biomarkers have limited diagnostic sensitivities and specificities,

analysis of combinations of several biomarkers offers the possibility of enhanced diagnostic accuracy. The Institute for Systems Biology (ISB) has optimized the detection of parasite protein signatures in patient sera which have the immense potential as diagnostic biomarkers and intend to extend the validation in Indian population on larger patient cohorts.

Training The training programs under the aegis of the IUSSTF Joint Proteomics Research Center conducted by the American counterparts in India have been methodically designed to allow the participants to experience an application-based workflow from sample preparation to data analysis. The participants attending the courses and training sessions are split into groups during the lab demonstration sessions, wherever required. The participants are mentored by Dr. Sanjeeva Srivastava and Dr. Joshua LaBaer in technologies for diagnostic applications; Dr. Srikanth Rapole for mass spectrometry analysis of samples and finally Dr. Robert Moritz for the computational analysis of proteomics data.

The training curriculum designed by the Center engages the participants in an interactive manner and are akin to a “Boot Camp”. Lectures and laboratory demonstration sessions are alternated to avoid exhaustion for the participants, and keep them involved. The program

Driving forces behind the project (from Left to Right) – Dr. Lee Hood (ISB, Seattle), Dr. Sanjeeva Srivastava (IIT Bombay) and Dr. Robert Moritz (ISB, Seattle)

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Feature

begins with the functional proteomics modules and gradually move towards the computational proteomics for data analysis. Each module will include introductory lectures covering the basics and advancements on the proteomics approach along with a typical workflow in the laboratory demonstrations including, sample preparation, data acquisition and data analysis. During the hands-on lab sessions, the participants are divided into smaller groups to allow better interaction of students with the instructors, providing a better learning experience. It will also help the instructor to alter the sessions a little, if required, depending on the experience and queries of the participants.

The IUSSTF Joint Proteomics Research Center has been highly successful with the exchange of scientists between India and the U.S. and have culminated in world-class courses and training session held at IIT Bombay. The Indian scientists involved in the Center have entered into new collaborations and have signed world class agreements in collaboration across many research goals.

The opportunity for young student researchers to travel to the U.S. and conduct research and training there as part of the Center has made an enormous impact in the student population in India and the attendance of the IUSSTF Joint Proteomics Research Center courses have been filled to capacity as a result. With the goals of the Center aimed at driving the efforts in training and collaborations, a bright future can be visualized for many young student scientists.l

Trans-Proteomic Pipeline (TPP) workshop conducted by ISB team at IIT Bombay in December 2018

Dr. Sanjeeva Srivastava (IIT Bombay) and his research team conducting high-throughput proteomics by SWATH mass spectrometry at Dr. Robert Moritz’s laboratory in ISB, Seattle

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GivingWINGS TO TALENT

To address the need for human resource development and capacity building in science and technology, IUSSTF is committed to nurture contacts between scientists and students from India and the United States. It has been unambiguously demonstrated that providing students and young scientists

with an exposure to cutting-edge scientific research experiences at a formative stage not only broadens their intellectual horizons but also leads to increased engagements in scientific and technological research careers. In this section of Connect, we share with you the experiences of some of our bright, young Interns and Fellows in their own words!

Student Speak

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Being a researcher in developmental neuroscience, I appreciate the significance of being in the right place at the right time. This is precisely what the

Indo-U.S. GETin internship provided me. This opportunity came at the right time during my Ph.D. allowing me to incorporate genetic editing techniques in my research and skillset. I visited the lab of Prof. Shawn Burgess at the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH), Bethesda, Maryland for my GETin internship. Beginning from the application process to my return after six months, the journey was a smooth sail and extremely rewarding experience.

The research atmosphere at NIH was very accommodating yet competitive with a keen emphasis on research ethics and biosafety training. Prof. Shawn and the lab members nurtured my research skills during the internship and supported me throughout the period. Apart from my main focus on learning

cutting-edge genome editing techniques, my stay at NIH was especially productive in terms of acquiring soft skills like networking, mentoring and collaborating with fellow scientists. Outside the lab, I regularly participated in hikes and social events organized by the Visiting Fellows Committee (VFC) where fellow international graduate students and PostDocs from all the institutes at NIH would interact. A mixed bag of culture, stories, cuisines and humour is how I would define these VFC events. Being close to Washington DC, I also had free access to the renowned Smithsonian museums and the various historic places around which were absolutely delightful. I stayed in the heritage town of Kensington which is very close to NIH and had a blast with people from all over the globe, who I was sharing the house with. Some special highlights of my stay were the unexpected snowfall in March and my visit to Philadelphia and New York City.

On a personal note, my visit to the U.S. has made me more confident socially and academically. I hope more people make use of this wonderful opportunity to expand the horizons of their science and self.l

Genome Engineering/Editing Technology Initiative Program (GETin Program)

Dhriti NagarIndian Institute of Science Education & Research (IISER), Pune

Student Speak

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Finally my dreams became a reality when I got the letter from IUSSTF stating that I was among the five candidates selected for the Indo-U.S. Genome

Editing Initiative (GETin) overseas fellowship program! I am a principal scientist working on plant viruses at Indian Agricultural Research Institute, New Delhi. Potentiality of this genome editing technology for management of plant viruses is trending and I got the opportunity to work in this field under the guidance of Dr. Hanu R. Pappu at Washington State University, Pullman, USA. Pullman is a very small picturesque university. During my six-month visit, I worked on application of genome editing technology for management of DNA viruses of plants. All the students and faculty were extremely cordial, knowledgeable and professional. Few things that I really appreciated about the lab was that the mentors and all the lab members always try to give importance to the novelty of research; procurement procedure for any items

for research was very simple; common and huge instrumentation facility and the availability of technological expertise majorly boost work progress; and the waste management systems are at the state-of-the-art level. The knowledge which I gained there can open up a new area of research in plant virology in India.

We visited many important places in USA during our stay. In the west coast we visited Las Vegas, Grand Canyon, Hollywood studio and Disney land in Los Angeles, Seaworld in San Diego, and Yellowstone National Park. In the east coast at Boston, I attended an International conference and along with Boston we visited New York, Washington D.C., Philadelphia and the Niagara Falls.lAnirban Roy

Indian Agricultural Research Institute New Delhi

GETin ProgramWebpage: https://www.iusstf.org/program/genome-engineeringediting-technology-initiative-program

E-mail: [email protected]

Student Speak

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Water Advanced Research and Innovation Program (WARI)

The challenge of providing water for drinking, growing crops, sanitation and industrial growth for over a billion people is daunting. To meet this challenge, India will need professionals

who are not only well versed in the latest developments of water science, but also have an understanding of the regional context that affects applicability of solutions to India. Programs such as the Water Advanced Research Internship (WARI) will go a long way in creating this pool of professionals by exposing students and faculty across India to international expertise in various areas of water science as offered at the University of Nebraska at Lincoln.

This was not obvious to me as I applied for the WARI fellowship. My main goal was to explore a collaborative opportunity with Prof. Ashok Samal, an expert in computer vision and data mining at the University of Nebraska at Lincoln (UNL). Being a

computational hydrologist, I knew I had a lot to learn from his years of experience in looking for patterns in large datasets. As I started my work with Prof. Samal, he offered that I also join in his weekly group meetings. I was initially apprehensive of the value of these meetings, however, they went on to become one of the most memorable exchanges at UNL. When social scientists, computer scientists and water scientists sit in the same room, the ensuing conversations head in directions that neither could have foreseen in their individual pursuits. This opportunity to interact with diverse professionals was the most valuable of my experience at UNL. Not to mention the fact that I met individuals working in water science in India that I had not had the benefit of knowing before.

My heart felt thanks to those who conceptualized this program. I thank Ms. Monika Madan (IUSSTF) and Mr. Jesse D. Starita (coordinator for WARI from UNL) for working out the logistics. I also thank Dr. Nicholas Brozovic at the Water for Food Institute for his useful insights on the economic context of water problems. Finally, I thank the Department of Computer Science at UNL for providing a productive office atmosphere. I feel we will need more of such programs if we hope to provide long lasting solutions to the water problems of India.l

Riddhi SinghIndian Institute of Technology Hyderabad

Water Advanced Research and Innovation ProgramWebpage: https://www.iusstf.org/program/water-advanced-research--innovation-fellowshipE-mail: [email protected]

Student Speak

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Dinesh BhardwajCSIR-National Physical LaboratoryNew Delhi

Being a research scholar in the field of solar energy in India, the Bhaskara Advanced

Solar Energy (BASE) Fellowship Program is a window for a Ph.D. student to experience the latest scientific research. I am very thankful to IUSSTF for giving me this excellent opportunity. Under this BASE fellowship I worked at Georgia Institute of Technology under the supervision of Prof. Seth R. Marder, Associate director of Center for Organic Photonics and Electronics (COPE) at Georgia Tech. As a result of this opportunity, I was able to design and developed PDI-based

non-fullerene acceptors for photovoltaic application. Also the valuable experienced gained at Professor Marder research’s group has developed my skills to synthesized electron transport layer (ETL) and hole transport layer (HTL) materials for perovskite solar cells and organic solar cell applications.

Professionally & personally I must say that it was a life-changing experience. I experienced snowfall first time in Atlanta city. I also visited Georgia aquarium, Swami Narayana temple and the ISKCON temple. I am proud to be the part of BASE internship program. For this I want to thank IUSSTF for providing me this great opportunity which has made me more confident and a better researcher.l

Bhaskara Advanced Solar Energy Fellowship (BASE) Program:Webpage: https://www.iusstf.org/program/bhaskara-advanced-solar-energy-fellowship

E-mail: [email protected]

Bhaskara Advanced Solar Energy (BASE) Fellowship Program

Student Speak

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Initiative for Research and Innovation in Science (IRIS) is a public – private partnership heralded by the Department of Science & Technology (DST), Intel and Indo-U.S. Science and Technology Forum (IUSSTF) for empowering the next generation of innovators held in India annually. IRIS is a research-based science fair initiative for school students. The winners of IRIS get an opportunity to be part of Team-India and represent the country at Intel International Science & Engineering Fair (ISEF) held in the U.S. every year. This year ISEF is being held from 13-17 May 2019 at Phoenix. Arizona, USA.

A Flag-off ceremony was held in New Delhi to wish the very best to Team-India for representing the country at ISEF 2019. This team, comprising of 25 bright young innovators was complimented for their participating projects by Chief guest Prof. K.VijayRaghavan, Principal Scientific Advisor to Govt. of India, and other dignitaries including Dr. Nisha Mendiratta, Head, NCSTC, Department of Science and Technology, Government of India, Dr. Anjan Ghosh, Global Director Corporate Affairs, Intel Corporation and Dr. Rajiv K. Tayal, Executive Director, IUSSTF. The audience, including these dignitaries, were

Initiative for Research and Innovation in Science

Young Turks

Feature

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quite impressed with the projects showcased at the event, most of which were aimed at providing workable solutions for societal problems. The scope of the projects ranged from devising a new method to screen Amblyopia; to using digital technology in form of an android application for effective waste management; to providing

low-cost, personalised and supplemental physiotherapy services to cervical spine patients etc.

Over the years, several of the young geniuses who participated in ISEF as part of Team-India, have won various Grand Awards including minor planets named after each of the Grand Award winner for their innovative projects.l

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With the unimaginable gain in computer power over the last decade, the next frontier in computational biology is to understand complex cellular

machinery by investigating the structure and dynamics at the molecular level. Despite the need, exploring the molecular properties is a daunting task. Experimental approaches are typically limited to a specific window of observable length and time scales. In contrary, integrated mathematical modelling and multiscale simulation approaches offer unparalleled strategies for exploring biological systems, a philosophy that may open up avenues to understand the etiologies of human diseases and supplement the known actionable findings and also can forecast possible ways of disease progression and resistance. However, the major challenge in such approaches is the sampling of molecular conformational states that often limits experiments to a biased outcome. This Indo-U.S. Symposium on Multiscale Simulation and Mathematical Modeling of Complex Biological Systems organized by Arnab Bhattacherjee (Jawaharlal Nehru University, New Delhi), Indira Ghosh (Jawaharlal Nehru University, New Delhi) and Anatoly B. Kolomeisky (Rice University, Texas) brought together researchers from the U.S. and India to discuss such challenges and the advances in the development of mathematical models and multiscale simulation techniques that have the potential to unravel the structure-function relations of cellular machinery. The major

focus was on the different methods for modelling the dynamics of biomolecular systems, ranging from force-field based all-atom representation of individual biomolecules to coarse-grained models for multicomponent systems. The symposium also provided hands-on training in workshop mode on the necessary practical knowledge of mathematical modelling and development of multiscale simulations of large and complex biological systems. The focal point was on the applications of multiscale models and simulation to gain insights into diseases with specific reference to cancer, genetic disorders and infectious diseases.

28 January - 01 February 2019New Delhi, INDIA

Events Diary

January-February, 2019

Multiscale Simulation and Mathematical Modeling of Complex Biological Systems

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India is a unique country featuring an enormous biodiversity and two global biodiversity hotspots - the Western Ghats and Eastern Himalayas. Much of this

biodiversity is interspersed with a large, rapidly expanding, human population. Along with the challenges of changes in land use, the Indian economy is also on the rise, which adds another set of challenges. Bioacoustics is a research field at

14-21 March 2019Tirupati, INDIA

Events Diary

March, 2019

Training Program in Bioacoustics

26-28 February 2019New Delhi, INDIA

February, 2019

Advancing Environmental

Health Science Research and Translation in India through Community-

based Participatory

Research (CBPR)

The 2018 Global E n v i r o n m e n t a l

Performance Index, a ranking based on 24 performance indicators for environmental health and ecosystem vitality, ranks India 177th in a list of 180 countries. Not surprising then that environmental risk factors are among

the top risk factors contributing to India’s disease burden. That health is closely interlinked with social and economic determinants is widely recognized, but, the evidence linking environmental exposures and health is limited in India. With rapid economic growth, India faces many environmental challenges, which are affecting the health and quality of life of its population. Improving environmental health research and its translation to practice in India is essential to address its environmental health burden of disease. To achieve this, traditional investigator-led academic research methods will not suffice. This Indo-U.S. Workshop on Advancing Environmental Health Science Research and Translation in India through Community-based Participatory Research (CBPR) organized by Rajesh Tandon (Society for Participatory Research in Asia, New Delhi), Banalata Sen (Society for Participatory Research in Asia, New Delhi) and Edith Parker (University of Iowa College of Public Health, Iowa City) highlighted the use and benefits of CBPR methodology in environmental health research; showcased different approaches to participatory research; aimed to evolve an environmental health focused CBPR framework relevant for India; and identify collaborative Indo-U.S. CBPR projects to address some of India’s pressing environmental health challenges.

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At the core of Internet-of-Things (IoT) is sensor technology. The development of discrete sensor technology and data collection has created extensive datasets

to understand the environment and enables accurate predictions. The concept was introduced in the early 2000’s that primarily focused on data collection, management, and connectivity. The sensor nodes that are at the bottom end of the IoT architecture are implemented with the off-the-shelf physical and chemical sensors that are not necessarily optimal. A sensor node consists of energy modules, power management modules, RF modules, and sensing modules. Each listed modules should be designed to deliver the highest performance with the lowest energy. It is impossible to achieve the required performance and energy specification with improvement in a single module. Though power and communication modules are well explored for IoT application, development of sensor technology is barely addressed. This Indo-U.S. Workshop on Sensor Technology for Next Generation IoT organized by Shankar Kumar Selvaraja (Indian Institute of Science, Bengaluru) Shiv Govind Singh (Indian Institute of Technology Hyderabad), Mike A. Carpenter (SUNY Polytechnic Institute, New York), and Thomas Thundat (University at Buffalo, New Yprk) discussed in detail physical sensor, chemical sensors, and optical sensor requirements and current status and future specific to IoT application. In addition, the workshop also focused on the packaging and connectivity aspects as well. Overall, the workshop was designed to discuss and deliberate the requirements and propose breakthrough technology that could be taken-up further for execution.

15-16 March 2019Bengaluru, INDIA

March, 2019

Sensor Technology for Next Generation Internet-of-Things

the intersection of physics, biology, ecology, and natural history. It can have various applications; in describing new species of various taxa, in helping understand genetic diversity, in understanding cultural diversity, and providing insights into behaviour and behavioural ecology of various organisms. Bioacoustics has also been used to understand the ecological impacts of deforestation and landscape change. With recent technological innovations, bioacoustics has grown to incorporate new automated recording techniques and innovative acoustic analyses that allow examinations of changing soundscapes and the resulting impact on biodiversity and animal habitats. Although research in biology in India has been rapidly increasing, bioacoustics has had limited capacity in the Indian subcontinent, and there are very few research

groups in the country working in this field. RAVEN is a commercially available software developed by Cornell University, and is arguably one of the most popular software being used by the community. This Indo-U.S. Training Program on Bioacoustics organized by Robin Vijayan (Indian Institute of Science Education and Research Tirupati), Padmanabhan Rajan (Indian Institute of Technology Mandi) and Holger Klinck (Cornell Lab of Ornithology, Cornell University, Ithaca) invited researchers and trainers from Cornell Lab of Ornithology’s Bioacoustics Research Program and Macaulay Library to IISER Tirupati to demonstrate and train students in RAVEN. They also demonstrated various recording techniques using hand-held recorders and with their own recorder SWIFT.

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Events Diary

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Indo-US Science and Technology Forum: Catalysing Indo-US Science & Technology Cooperation over a decade.

For program details visit:

http://www.indousstf.org

Indo-US Science & Technology ForumThe Indo-US Science and Technology Forum (IUSSTF), established under an agreement between the Governments of India and the United States of America, is an autonomous, not for profit society in India, co-funded and co-governed by both the governments. IUSSTF promotes and catalyzes Indo-US collaborations in science, technology, engineering, biomedical research and innovation through substantive interaction among government, academia and industry.

Foster excellence by capitalizing on the scientific and technological synergyDisseminate information and create awareness through scientific exchangesBuild linkages through networking between academia and industryExplore new frontiers by nurturing contact between young and mid-career scientists Pave way to sustainable interactions and establish long term relationshipsEncourage public-private partnership to inculcate elements of innovation and entrepreneurship

Academia-Industry Connect ProgramsAdvance Schools & Training ProgramsBilateral Workshops & SymposiaFlagship EventsKnowledge R&D Networked Joint Centers

Programs on Innovation and EntrepreneurshipPublic-Private Networked R&D Joint CentresResearch Fellowships for FacultySpecial Initiatives for Strategic PartnershipsStudent Internships & Visiting Professorships

Exciting and innovative collaborative programs cutting across disciplines and institutions

What we do

Who we are

We support

We invite

How to contact us?

Indo-US S&T Forum

IUSSTF

Proposals which are peer reviewed both in India and USA for awards Bilateral Indo-US Workshop/Symposia & Indo-US Training/Advanced SchoolsSubmission Deadlines Award Announcements15 February 30 June15 August 31 December

Indo-US Public-Private Networked Centres & Indo-US Knowledge R&D Networked CentresSubmission Deadline Award Announcement15 August 31 December

Submission Deadlines Award Announcements1 March 31 July31 August 31 January

Submission Deadline Award Announcement31 August 31 January

IUSSTF: Catalysing Indo-US Science, Technology and Innovation Collaborations for 18 Years!Indo-US Science and Technology Forum:

Catalysing Indo-US Science & Technology Cooperation over a decade.

For program details visit:

http://www.indousstf.org

Indo-US Science & Technology ForumThe Indo-US Science and Technology Forum (IUSSTF), established under an agreement between the Governments of India and the United States of America, is an autonomous, not for profit society in India, co-funded and co-governed by both the governments. IUSSTF promotes and catalyzes Indo-US collaborations in science, technology, engineering, biomedical research and innovation through substantive interaction among government, academia and industry.

Foster excellence by capitalizing on the scientific and technological synergyDisseminate information and create awareness through scientific exchangesBuild linkages through networking between academia and industryExplore new frontiers by nurturing contact between young and mid-career scientists Pave way to sustainable interactions and establish long term relationshipsEncourage public-private partnership to inculcate elements of innovation and entrepreneurship

Academia-Industry Connect ProgramsAdvance Schools & Training ProgramsBilateral Workshops & SymposiaFlagship EventsKnowledge R&D Networked Joint Centers

Programs on Innovation and EntrepreneurshipPublic-Private Networked R&D Joint CentresResearch Fellowships for FacultySpecial Initiatives for Strategic PartnershipsStudent Internships & Visiting Professorships

Exciting and innovative collaborative programs cutting across disciplines and institutions

What we do

Who we are

We support

We invite

How to contact us?

Indo-US S&T Forum

IUSSTF

Proposals which are peer reviewed both in India and USA for awards Bilateral Indo-US Workshop/Symposia & Indo-US Training/Advanced SchoolsSubmission Deadlines Award Announcements15 February 30 June15 August 31 December

Indo-US Public-Private Networked Centres & Indo-US Knowledge R&D Networked CentresSubmission Deadline Award Announcement15 August 31 December

www.iusstf.orgFor program details visit:

Indo-US Science and Technology ForumFulbright House 12 Hailey Road, New Delhi - 110 001