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New Delhi Cape TownTrieste
ICGEB Cape Town 2007-2011
The first four years of the ICGEBCape Town Component, South Africa
ICG
EB
ICGEB Cape Town
New Delhi Cape TownTrieste
ICGEB Cape Town 2007-2011The first four years of the ICGEB
Cape Town Component, South Africa
ICGEB Cape Town
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Nippostrongylus brasiliensis. A nematode used to understand the immuneresponse to gastrointestinal worms. This image shows a female worm containing eggs.
There is increasing international recognition that science- and technology-intensive solutions can significantly improve quality of life. This is particularly true where biotechnology is concerned, since this field is of paramount interest for health (including the development of new medicines, vaccines and diagnostic procedures), agriculture (through the generation of biotic- and abiotic-stress resistant crops and plants with improved nutritional value), and the environment (by reducing waste and pollution).
To be effective, such research-driven solutions, however, must not be restricted to developed countries, but need to be directly implemented in developing countries themselves. Towards this goal, a serious effort is required to build human capacities through a global approach, which includes training in science and in the applications of science, fostering innovation, building entrepreneurship and valuing intellectual property.This is of particular relevance
for Africa, a vast continent with variegated geography, cultures, resources, strengths and weaknesses. Africa still pays an outrageously high death toll to infectious diseases such as malaria (700,000 children under the age of 5 die every year), or HIV/AIDS (where every 12 hours, 3,000 people die of this disease). In Africa, hunger or malnourishment affect one third of the population. In addition, non-communicable diseases are also increasing at an alarming rate.
All of these are issues that can be effectively tackled through a science-based approach focusing on research and its biomedical and agricultural applications.Capacity building of young African scientists on topics of direct relevance to the major health and agricultural problems of the continent is the ultimate mission of the Cape Town Component of the International Centre for Genetic Engineering and Biotechnology.
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Biotechnologyfor Africa
New Delhi Cape TownTrieste
ICGEB Cape Town
ICGEB, established in 1987, is an international, intergovernmental organisation conceived as a Centre of excellence for research and training with special regard to the needs of the developing world. The Centre conducts innovative research in life sciences and strengthens the research capability of over 60 Member States through training, funding programmes and advisory services.
The ICGEB Component laboratories, located in Trieste (Italy), New Delhi (India) and Cape Town (South Africa), provide a scientific and educational environment of the highest international standard. ICGEB offers postgraduate and postdoctoral fellowships; an international PhD Course is run in all three ICGEB Components. Over 20 practical and theoretical courses are organised every year
on subjects at the forefront of modern biology and biotechnology. Policy guidelines on the use of ICGEB-owned intellectual property rights and know-how foster innovative approaches to industrial relations at a global level and enhance joint ventures for the commercialisation of biotechnology research.
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The International Centre for Genetic Engineering and Biotechnology
Why ICGEBICGEB is a unique research institution blending high standard academic goals, focus on developing countries and a mandate on capacity building.In its three Components, cutting-edge research is carried out, with scientific excellence as a major goal.
Activity is spearheaded by an International Scientific Advisory Council of top scientists and Nobel laureates from across the world.Research focuses on issues of utmost relevance for developing countries, including HIV/AIDS, malaria, tuberculosis, plant
biotechnology, as well on basic research topics. Intellectual property rights generated by ICGEB research can be shared by its Member countries; specific programmes are in place to directly transfer technologies to these countries.
ICGEB Cape Town
Currently, the premises of the ICGEB Cape Town Component cover around 1,200 square metres on the University of Cape Town, Health Science Faculty Campus, and host the activity of four Research Groups. The Component operates research programmes at the forefront of scientific excellence, constituting the basis upon which the training programmes are implemented. Current research focuses on
infectious diseases (HIV, malaria, tuberculosis, trypanosomiasis, leishmaniasis and schistosomiasis) and non communicable diseases (cancer). A Biotech Transfer Unit for the development of technologies for biogeneric pharmaceuticals, industrial enzymes and other bio-molecules with potential industrial applications, has also been established. New Research Groups, including one dedicated
to agricultural biotechnology, will become operational within the next two years.While no single institution can tackle the majority of problems and scientific needs of the African continent, ICGEB Cape Town aims to provide a training platform in topics and techniques that the trained scientist will later implement in disparate fields of research and development.
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The ICGEB Cape Town Component
Research and training laboratories at the ICGEB Cape Town Component access state-of-the art instrumentation for advanced molecular and cell biology applications, and include ICGEB-owned equipment as well as facilities shared with the Institute for Infectious Disease and Molecular
Medicine (IIDMM) of the University of Cape Town. These include resources for cell culture and flow cytometry; advanced optical confocal microscopy; a BSL-3 safety laboratory for the handling of class-3 pathogens; a bioexperimentation facility, fully equipped with survival surgical suites, housing for conventional specific
pathogen-free (SPF), viral antibody-free (VAF) and immunodeficient rodents. Shared equipment and resources include facilities for imaging, DNA synthesis, viral vector production, radioisotope handling, and access to the Centre for Genomics and Proteomics.
Established in September 2007 with the aim to specifically strengthen the ICGEB activities on the African Continent, the focus of the research undertaken at the ICGEB Cape Town Component is geared to address key needs of the African population. Each activity contains a major training component aimed at tackling some of the key issues identified through the Millennium Development Goals.
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ICGEB Cape Town
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There are approximately 70 people operating at ICGEB Cape Town, of whom more than 60 are scientists in the laboratories.
Personnel
ROLe
GeNDeR
48%
7%3%
44% 46%52%
41%
6% 12%
6%
12%
24%
LeVeL OF eDUCATION
AGe
Male Female
Phd University High School
Group LeaderStaff ScientistPost-docPhD StudentTechnicianStudent
39%
24%
37%
<30 30-40 40-50 >50
New Delhi Cape TownTrieste
Two thirds of these originate from African countries, as shown on the map above, where the countries of origin are indicated as circles
(the larger the circle, the higher the number of people from that country). Over 20 fellows and students are funded through
the University of Cape Town.The pie charts show the division of personnel according to role, level of education, gender and age.
ICGEB Cape Town
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Training
Teaching and contributing to a vibrant research community in Cape Town and elsewhere across Africa are concepts integral to the activities of the ICGEB Cape Town Component.Pre-and postdoctoral fellowship programmes offer high-profile, multidisciplinary training and cover a range of topics in genetic engineering and biotechnology. The PhD Programme is carried out in conjunction with the University of Cape Town. African scientists from ICGEB Member States are eligible to apply for fellowships. Full details for
applications are available on the Web site.Additional activities include student exchange programmes with the Royal Society, UK, the National Research Foundation, Zaire, the University of Strathclyde and the University of Glasgow, UK, the University of Wuerzburg, Germany and the University of Stellenbosch, South Africa. Furthermore, in the
framework of its biosafety activities, ICGEB has funded 16, one-year MSc fellowships in “Risk Assessment of GM Crops”, dedicated to sub-Saharan African students, at the University of Aberystwyth (UK).The EU-FP7 funded PRD college involves collaborative training programmes between Cape Town, Italy, Sweden, Cameroon, Tanzania, Uganda, Zambia and Zimbabwe.
The ICGEB training programmes have funded over 70 African postdocs and PhD students since 1989, across 18 African countries.One of its success stories follows Dr. Joseph Bigirimana who returned to his native Burundi in 2007, setting up several rice-bacterial working models. He has moved on to become the
Dean of the Faculty of Agriculture at the University of Bujumbura and is now Liaison Scientist and Coordinator for the International Rice Research Institute (IRRI) in Burundi.The map shows the countries of origin of the ICGEB African fellows (the larger the spot, the higher the number of people from that country).
African fellows at the ICGEB Components
PhD & Postdoc Fellowships: http://www.icgeb.org/fellowships.html
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Every year, the ICGEB organizes over 20 meetings, workshops and courses in its Components
and Affiliated Centres worldwide, covering subjects at the forefront of biomedical research and
biotechnology. Many of these educational activities are held in Africa, such as those listed below.
Theoretical Course “Global Infectious Disease Research: a multidisciplinary approach”
4-10 September, 2011 - Cape Town, South Africa
Workshop on “Parasitic Infection and Inflammation” 23-26 March, 2011 - Cape Town, South Africa
Argentina Joint Regional Biosafety Workshop “Biosafety of GM Crops: Emerging Issues and Challenges Affecting Regulatory Decision Making”
7-11 March 2011 - Pretoria, South Africa
Joint International Conference of the African and Southern African Societies of Human Genetics
6-9 March 2011 - Cape Town, South Africa
Workshop on “African Trypanosomiasis” 19-22 October, 2010 - Cape Town/Franschhoek, South Africa
ICGEB/IUBMB “Genomics and Proteomics Approaches in Cancer Research”
5-11 September, 2010 - Cape Town, South Africa
Workshop on “Tuberculosis transcriptomics” - 26-28 June, 2010 - Cape Town, South Africa
Theoretical and Practical Course “Molecular Modelling and Structure-Function Relationships Studies of Enzymes of Biotechnology Interest”
19-24 April, 2010 - Sfax, Tunisia
Second Advanced Summer School in Africa, Training Course on the “Molecular Mechanisms of Viral Infection and Propagation”
6-14 March, 2010 - Hermanus, South Africa
Workshop on “Recent Advances in Biotic Stress Tolerance in Plants” 13-20 February, 2010 - Cairo, Egypt
Theoretical Course “Molecular Medicine and Genomics in Africa” 28-31 January, 2010 - Zanzibar, Tanzania
“Current Topics on Tropical and Emerging Infectious Diseases: Protozoan Pathogens Comparative Genomics Workshop”
14-18 December, 2009 - Ibadan, Nigeria
Theoretical and Practical Course “Fungal Genomics” 12-18 July, 2009 - Abekouta, Nigeria
Theoretical and Practical Course “Genetic Transformation System in Insects”
12-17 July, 2009 - Suez, Egypt
The 1st Annual Meeting of the Cameroonian Society of Human Genetics 12-15 March, 2009 - Yaoundé, Cameroon
Workshop on “New molecular and nano-technologies to visualize and analyses host/pathogen interactions and inflammatory processes”
10-13 December, 2008 - Cape Town, South Africa
Workshop on “Risks, benefits and opportunities from the release of GMOs in the African regions”
15-19 September 2008 - Cape Town, South Africa
International Symposium on Biotechnology 4-8 May, 2008 - Sfax, Tunisia
International conference on “Immunology of Health and Disease” 9-14 March, 2008 - Cape Town, South Africa
The Molecular and Cellular Basis of Infection 29 February-9 March 2008 - Cape Town, South Africa
Theoretical Course “Molecular Medicine and Genomics in Africa” 19-24 January, 2008 - Khartoum, Sudan
Regional Workshop on “Principles of Biosafety Research for the Release of Genetically Engineered Crops (Plants)”
1-8 September, 2007 - Giza, Egypt
Theoretical and Practical Course “Theoretical and Practical Training Workshop in Proteomics and Protein Bioinformatics”
9-13 July, 2007 - Limpopo, South Africa
Regional Workshop on “Principles of Biosafety Research for the Release of Genetically Engineered Crops”
4-9 February, 2007 - Khartoum, Sudan
Meetings & Courses: http://www.icgeb.org/meetings-and-courses.html
ICGEB Meetings and Courses in Africa 2007-2011Every year, the ICGEB organizes over 20 meetings, workshops and courses in its Components and Affiliated Centres worldwide, covering subjects at the forefront
of biomedical research and biotechnology. Many of these educational activities are held in Africa, such as those listed below. Researchers from institutes in
ICGEB Member States throughout Africa can apply for financial support to organise meetings and workshops. Criteria for eligibility are available on the Web site.
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Biosafety
The ICGEB Biosafety Unit, working primarily out of the Cape Town Component, organizes practical workshops, offers fellowships and provides funds to encourage participation in regional and international conferences, developing and fostering links with the international scientific community.
This activity is performed in the framework of a 3 million US dollar project funded by the Bill & Melinda Gates Foundation to help support the development of effective safety and regulatory systems for biotechnology in Africa.Since 2008, ICGEB has granted postdoctoral and research
fellowships to attend the MSc course “Managing the Environment” at the Aberyswyth University, UK to sub-Saharan nationals.More than 100 scientists and regulators from Sub-Saharan Africa have been trained at workshops, while over 30 participants have attended regional and international
conferences, such as the International Symposium on the Biosafety of Genetically Modified Organisms (ISBGMO) and the Conference of the Parties to the Convention on Biological Diversity Serving as the Meeting of the Parties to the Cartagena Protocol on Biosafety (COP-MOP).
ICGEB Biosafety Workshops in Africa
A Discussion of the Key Elements in GMO Regulation Dec 2011 - Kigali, Rwanda
Confined Field Trials (CFTs) for Genetically Modified Crops: a Theoretical and Practical Course for Regulators, Applicants, Reviewers and Inspectors of CFTs
5-9 Sep 2011 - Bobo-Diulasso, Burkina Faso
Stakeholder Workshop on Biosafety Risk Communication 8-10 Jun 2011 - Quatre Bornes, Mauritius
Biosafety of GM Crops: Emerging Issues and Challenges in Regulatory Decision Making
7-11 Mar 2011 - Pretoria, South Africa
Risk Analysis for the General Release of Genetically Modified Crops 14-18 Dec 2010 - Nairobi, Kenya
Confined Field Trials (CFTs) for Genetically Modified Crops: a Theoretical and Practical Course for Regulators, Applicants, Reviewers and Inspectors of CFTs
30 Aug-3 Sep 2010 - Accra, Ghana
Theoretical Approaches and their Practical Application in the Risk Assessment for the Deliberate Release of Genetically Modified Plants”
22-26 Mar 2010 - Hermanus, South Africa
Introduction to GMO Biosafety Risk Assessment 19-23 Oct 2009 - Kampala, Uganda
Biosafety: http://www.icgeb.org/~bsafesrv/
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Grants 2007 - 2011
In addition, funding for research and technology transfer has been generated from various external sources, including the Bill & Melinda Gates Foundation and the Carnegie
Foundation, USA; the Wellcome Trust and the Royal Society, UK; the European Commission; UNESCO; the National Research Foundation and Medical Research
Council of South Africa, among others. The charts below show the grants obtained from 2007 to April 2011 and indicate those already secured up to 2014.
Number of grants 32
Total amount awarded (Euro) 3,847,800
Average number of active grants per year 17.6
The generous contribution from the Government of South Africa, through the Department of Science and Technology, and the voluntary contribution from the Government of Italy, through the Ministry of Foreign Affairs, have allowed implementation of most of the training and scientific activities at the ICGEB Cape Town Component.
Funding
Core Budget External Funds
SOURCe OF FUNDINGN. ACTIVe GRANTS
Government/Public Bodies Charities/Foundations International OrganizationsPrivate Companies
6
236
560
779 763705
545
158101
07
07
0
0
5
200
10
400
600
800
15
20
25
08
08
09
09
10
10
(11)
(11)
(12)
(12)
(13)
(13)
(14)
(14)
18
2123
20
13
5
1
YEAR
YEAR
46% 54%
19%
16%
3%
63%
AMOUNT/1000 (€)
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Centre International de Réference Chantal Biya (CIRCB), Yaounde
Institut de Recherche Medicale et d’Etude des Plantes Medicinales (IMPM), Yaounde
Cameroon
EIPICO - Egyptian International Pharmaceutical Industries CO Egypt
Kenya Medical Research Institute (KEMRI) Kenya
Centro de Investigação em Saúde Mozambique
University of Maiduguri Teaching Hospital Nigeria
University of Cape Town
University of Stellenbosch
South African Pharmaceuticals
South Africa
University of Khartoum
University of Gezira
Sudan
Ifakara Health Institute
National Institute for Medical Research
Tanzania
Institute Pasteur
Centre of Biotechnology - Sfax
Tunisia
Makerere University Uganda
Technology Transfer
ICGEB Collaborations and Technology Transfers across the African Continent
Transfer of technologies is one of the most relevant activities of ICGEB.
The list below includes Institutes or Companies in Africa to which
technologies developed at ICGEB have been transferred.
Biotechnology Transfer: http://www.icgeb.org/biotechnology-transfer.html
Nippostrongylus brasiliensis. Gravid female nematode worms surrounded by bubbles with a hooked posterior end and eggs.
International scientific collaborations with the ICGEB Cape Town Component
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University of Melbourne Australia
Ludwig Institute for Cancer Research
University of Brussels
Belgium
Centro Infantil Boldrini, Sao Paulo Brazil
University of Helsinki Finland
University of Orleans France
University of Wurzburg
Forschungszentrum Borstel
University of Leipzig
University of Heidelberg
Technische Universität München
Heinrich Heine University, Düsseldorf
Germany
University of Pisa Italy
RIKEN Institute Japan
University of Wellington New Zealand
University of Oslo Norway
King’s College, London
MRC Mill Hill, London
University of Strathclyde, Glasgow
University of Glasgow
UK
University of Cincinnati, OH
UCSF, San Francisco, CA
Harvard Medical School and BIDMC Genomics Centre, Boston, MA
University of Michigan, MI
University of Rochester, New York, NY
Yale University, New Haven, CT
Virginia Commonwealth University, Richmond, VA
Massey Cancer Center, Richmond, VA
USA
Collaborations
Since 2007, under the ICGEB Grants programme, fourteen grants have been awarded to fund projects undertaken in African scientific institutes, for a total of half a million Euro, a number of which co-funded with the Academy of Science for the Developing World (TWAS).
ICGEB Grants to African Laboratories
ICGEB funding is available for research in Africa through its Collaborative Rese-arch Programme - a unique source of funding aimed at financing projects
addressing original scientific questions that show a potential contribution of particular relevance for the applicant’s country. A call for applications is
launched yearly and full information is available on the Web site. International collaborations with the ICGEB Cape Town Component are shown below.
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Total number of scientific publications 61
Number of publications with Impact Factor >8.0 6
Average number of publications per year 19.5
Number of publications per ICGEB-funded personnel
2.5
Total Impact Factor 332.6
Average Impact Factor per year 94.8
Average Impact Factor per Publication 5.5
Publications
ICGEB publishes results from its research in international, peer-reviewed scientific journals with high Impact Factor. Statistics show the number of publications authored to date by scientists from the ICGEB Cape Town Component.
Publications 2008-2011
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ICGEB Cape Town
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Research Research Group: Cancer Molecular and Cell Biology
Our epidemiological studies focus on the combined effects of genetic polymorphisms in the detoxification genes (cytochrome p450, glutathione-S-transferases) and exposure to environmental mutagens and carcinogens to the risk of developing OSSC. The Group is performing genome-wide association studies to identify SNPs that confer increased risk to OSCC.Human Papilloma Virus (HPV) DNA has been shown to be present in about 40% of South African tumour
biopsies. We are investigating the role of HPV in the aetiology of this cancer and its effects on normal cellular genes. Our interest in tumour cell invasion and metastasis centres around the degradation and remodelling of the extracellular connective tissue proteins. The role of tumour cells in the production of extracellular matrix proteins by normal stromal fibroblasts is being investigated by analysing the signal transduction pathways and the transcription
factors regulating the expression of the type I collagen genes (one of the extracellular matrix proteins).Finally, we developed a series of ajoene-based analogues that have been shown to be very effective in killing tumour cells in vitro. These analogues will be tested in animal models and studies are also underway to investigate the mode of action of these drugs.Contact:
Group Leader: Iqbal Parker
SELECTED PUBLICATIONS Li, D-P., Dandara, C. and Parker, M.I. (2010). Genetic Polymorphisms in the Glutathione S-Transferase Genes (GSTM1, T1 & P1) and Oesophageal Cancer Susceptibility. BMC Genetics, 11; 47-56.Kaschula, C, Hunter, R and Parker, MI (2010). The anti-cancer activity of ajoene: the use of chemically synthesised stable analogues. Biofactors, 36, 78-85Abrahams A, Parker M.I., and Prince S. (2010). The T-box transcription factor Tbx2: Its role in development and possible implication in cancer. IUBMB-Life, 62, 92-102Torniainen, S., Parker, M.I., Holmberg, V., Lahtela, E., Dandara, C. and Jarvela, I. (2009). Screening of variants for lactase persistence/non-persistence in populations from South
Africa and Ghana. BMC Genetics 10; 1-5Wang, B, Khachigian, LM, Birrer, MJ, Esau, L, Zhou, X. Parker, MI and Hendricks, DT. (2009). A key role for mediating and Maintaining GRO/CXCR2 proliferative signalling in oesophageal cancer. Mol. Cancer. Res. 5; 755-764Van der Watt PJ, Maske CP, Hendricks DT, Parker MI, Denny L, Govender D, Birrer MJ, Leaner, VD. (2009). The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer. 124,1829-1840.Teng, H., Parker, M.I. and Prince, S. (2008). Functional characterization of cis-acting elements involved in basal transcription of the human Tbx2 gene: A new insight into
the role of Sp1 in transcriptional regulation. Gene, 423, 8-13Abrahams, A, Mowla, S, Parker, M.I., Goding, C.R. and Prince, S. (2008). UV Mediated Regulation of the Anti-Senescence Factor, Tbx2. J. Biol. Chem. 283, 2223-2230Donninger, H, Binder, A, Bohm, L and Parker, MI. (2008). Differential Effects of Novel Tumour- Derived p53 Mutations on the Transformation of NIH 3T3 Cells. Biol. Chem, 389, 57-67Copley, L., van der Watt, P., Wirtz, K.W., Parker, M.I. and Leaner, V.D. (2008). Photolon(tm), a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis. Int. J. Biochem. & Cell Biol. 40, 227-35
The interests of this Group span epidemiology and molecular lesions in cancer, with particular reference to oesophageal squamous cell carcinoma (OSSC), one of the most common and devastating cancers in Eastern and Southern Africa.
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Research Research Group: Cytokines and Disease
Allergic asthma and colitis are chosen, non-infectious disease models under investigation. Major topics include cytokine network regulation; the significance of genes, factors and cells for host protection are uncovered, supporting our long-term goal for the development of safe and cost-effective drug and vaccination strategies.Recently, we demonstrated that
IL-4/IL-13-activated alternative macrophages are essential to survive acute schistosomiasis due to downregulation of T helper 1 cell responses to avoid hyperinflammation and sepsis. In addition, we demonstrated that IL-4/IL-13-induced smooth muscle cell hypercontractility contributes to resistance facilitating expulsion of schisto-eggs as well as gut-dwelling helminthes. In
cutaneous leishmaniasis, caused by L. major, activated alternative macrophages reduced protection due to their downregulating influence on protective Th1 responses. The same cells can cause uncontrolled cerebral cryptococcosis and influence experimental autoimmune encephalitis.Contact:
Group Leader: Frank Brombacher
SELECTED PUBLICATIONS Guler R, Afshar M, Arendse B, Parihar SP, Revaz-Breton M, Leitges M, Schwegmann A, Brombacher F. (2011) PKC_ regulates IL-12p40/p70 production by macrophages and dendritic cells, driving a type 1 healer phenotype in cutaneous leishmaniasis. eur J Immunol. 41:706-15. Dewals B, Hoving JC, Horsnell WG, Brombacher F. (2010). Control of Schistosoma mansoni egg-induced inflammation by IL-4-responsive CD4(+)CD25(-)CD103(+)Foxp3(-) cells is IL-10-dependent. eur J Immunol. 40:2837-47 Herbert DR, Yang JQ, Hogan SP, Groschwitz K, Khodoun M, Munitz A, Orekov T, Perkins C, Wang Q, Brombacher F, Urban JF Jr, Rothenberg ME, Finkelman FD. (2009). Intestinal epithelial cell secretion of RELM-{beta}
protects against gastrointestinal worm infection. J exp Med. 21:206:2947-57 Dewals, B., J. C. Hoving, M. Leeto, R. G. Marillier, U. Govender, A. J. Cutler†, W. G.C. Horsnell, F. Brombacher. (2009). IL-4R responsiveness of non-CD4 T cells contributes to resistance in Schistosoma mansoni infection investigated in pan-T cell-specific IL-4R_-deficient mice. J Am Pathol. 175:706-16 FANTOM Consortium. (2009). The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nature Genetics 41:553-62 Horsnell, W.G., F. Brombacher. (2008) Key roles for specific and nonspecific antibody in intestinal nematode expulsion. Cell Host Microbe 16:303-5 Barkhuizen, M., S Magez, B Ryffel and F
Brombacher. (2008). Interleukin-12p70 Deficiency Increases Survival and Diminishes Pathology in Trypanosoma congolense Infection. J. Infect. Dis 198:1284-91. Barbi, J, F. Brombacher, AR Satoskar. (2008). T cells from Leishmania major-susceptible BALB/c mice have a defect in efficiently up-regulating CXCR3 upon activation. J. Immunol. 181:4613-20 Magez, S., A. Schwegmann, R. Atkinson, F. Claes, M. Drennan, P. De Baetselier, and F. Brombacher. (2008). The role of B-cells and IgM antibodies in paratemia, anemia, and VSG switching in T. brucei-infected mice. PLoS Pathogens, 4:e000122 Schwegmann, A & F. Brombacher. (2008). Host-directed drug targeting of factors hijacked by pathogens. Science Signaling 1:29-36.
We investigate host protective mechanisms in diseases relevant to Africa. This comprises experimental murine models for tuberculosis, African trypanosomiasis (sleeping sickness), leishmaniasis and schistosomiasis (bilharzia), four of the top ten WHO declared threats to human health.
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Research Research Group: Cellular Immunology
Our research interests cover the role of antibody responses in protection against human immunodeficiency virus (HIV-1) and P. falciparum malaria. We focus on three major topics within this area. (1) The development of human monoclonal antibodies that broadly neutralise various strains of HIV-1. Evidence supports neutralising antibody as an important mechanism for protection by a future HIV vaccine. However, there is not enough information about the targeting of neutralising antibodies that are effective against a broad range of HIV isolates (“broadly neutralising
antibodies”) to successfully inform vaccine design. To date, most of the research activity isolating neutralising monoclonal antibodies has focused on antibodies from clade B-infected donors, in spite of the fact that approximately half of the HIV infections worldwide are clade C infections including most infections in Southern Africa. (2) Cloning and characterising HIV-1 subtype G envelope genes and their sensitivity to antibody-mediated neutralisation. This project targets currently under-studied subtype G viruses, which infect about 1.5 million people, mostly in West
Africa. This project will identify potential rational drug design targets and identify high priority vaccine targets for both HIV and malaria. (3) The development of human monoclonal antibodies against P. falciparum proteins forced to the surface of the infected red blood cell. Understanding the targets of natural immunity to pregnancy-related malaria in this project will lead to important vaccine antigen candidates for this disease.Contact:
Group Leader: Jeffrey Dorfman
SELECTED PUBLICATIONS Veiga J, Feinerman O, Dorfman JR, Germain RN, Altan-Bonnet, G (2008) Phenotypic variability of T cell signaling reveals flexibility in self/non-self discrimination. Science. 321(5892):1081-4Oleinikov AV, Francis SE, Dorfman JR, Rossnagle E, Balcaitis S, Getz T, Avril M, Gose S, Smith JD, Fried M, Duffy PE. (2008) VAR2CSA domains expressed in E.coli induce cross-reactive antibodies to native protein. J. Infect. Dis. 197(8):1119-23
HIV and Plasmodia induce striking antibody and T cell responses in humans. Nonetheless, much of this response is not protective to the host, hampering the design of an effective vaccine.
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ICGEB Cape Town
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Research Research Group: Cancer Genomics
We have identified the Cdk11p58, DEDD and DCN-1 as GADD45-interacting proteins. Cdk11p58 is a Ser/Thr kinase that participates in cell cycle progression and is inhibited by GADD45. A second project relates to the elucidation of the molecular mechanisms of cancer apoptosis induction by structurally different Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). The hypothesis is that NSAIDs and its chemically modified versions could act more specifically
against cancer, with less adverse reactions. The results so far obtained have established mda-7/IL-24 as a crucial mediator of NSAID-induced apoptosis in cells.Another project is the identification of cell surface receptors in cancer with particular focus on the tyrosine kinase receptor Axl. Our hypothesis is that targeting the AXL will inhibit cancer growth and thus lead to a novel therapeutic entry point for cancer. We have demonstrated
that Axl is upregulated in prostate cancer and colorectal carcinoma cell lines and clinical samples. Furthermore, we implicate Axl as a crucial regulator in proliferation, migration, and invasion of prostate cancer cells and tumor formation in vivo. Importantly, we are analysing a library of natural compounds originating from Africa and Asia with particular focus on Axl inhibition.Contact:
Group Leader: Luiz Zerbini
SELECTED PUBLICATIONS Tsuchimochi K, Otero M, Dragomir C, Plumb DA, Zerbini LF, Libermann TA, Komiya S, Ijiri K, Goldring MB. GADD45beta enhances Col10a1 transcription via the MTK1/Mkk3/p38 axix and activation of C/EBP beta-TAD4 in terminally differentiating chondrocytes. J Biol Chem 285(11):8395-407. 2010 Buffon A, Casali EA Cardoso VV, Zerbini LF, Robson SC, Sarkis JJ, Wink MR. Differential expression of nucleotide pyrophosphatase/phosphodiesterases by Walker 256 mammary cancer cells in solid tumors and malignant ascite. Life Science 86:435-40. 2010 Bruns I, Czibere A, Fischer JC, Roels F, Caded-du RP, Buest S, Bruennert DHuenerlituerkoglu4, NH Stoecklein AN, Singh R, Zerbini LF, Jager M, Kobbe G, Gattermann N, Kronenwett R, Brors B and Haas R The hematopoietic stem
cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence. Leukemia. 23:892-9. 2009 Cho JY, Lee M, Park ES, Ahn JM, Cho JH, Lee SJ, Kim BJ, Heo SH, Park HJ, Zerbini LF, Hwang D, and Libermann TA. Proteomic analysis of a PDEF Ets Transcription Factor-interacting Protein Complex. J. Proteome Res. 8:1327-37. 2009 Konstantinopoulos PA, Fount-zilas H, Zerbini LF, Pillay K, Libermann TA, Cannistra SA, Spentzos D. Carboplatin-induced gene expression changes in vitro are associated with survival in patients with epithelial ovarian cancer. BMC Genomics 1:59.2008 Dusek JA, Out HH, Wohlhueter AL, Bhasin M, Zerbini LF, Libermann TA, Benson H. Genomic Counter-Stress Changes Induced by a Mind Body Practice. Plos One 3: e2576. 2008.
Ijiri K, Zerbini LF, Peng H, Out HH, Tsu-chimochi K, Otero M, Dragomir C, Walsh N, Bierbaum BE, Mattingly D, Flandern G, Komiya S, Aigner T, Libermann TA, Goldring MB A Differential expression of GADD45 in normal and osteoarthritic cartilage: Potential role in homeostasis of articular chondrocytes. Arthritis and Rheumatism. 58: 2075-2087. 2008. Farinha-Arcieri LE, Carromeu C, Simabuco FM, Tamura RE, Zerbini LF, Ventura AM. Expression and purification of a recombinant adenovirus Fiber Knob in a baculovirus system. Intervirology. 51:189-195.2008 Rücker B, Almeida ME, Libermann TA, Zerbini LF, Wink MR and Sarkis JJ. Kinetic characteriza-tion and molecular identification of the nucleoti-de metabolizing ectoenzymes from rat heart left ventricle. Life Sciences. 82:477-86. 2008.
The Group is concerned with deciphering the molecular mechanisms of action of the GADD45 family of genes and their protein partners with the ultimate goal of identifying new molecular targets for cancer treatment.
New Delhi Cape TownTrieste
International Centre for Genetic Engineering and Biotechnology
ICGEB Cape Town ComponentWerner & Beit Building (South), UCT CampusAnzio Road - Observatory 7925Cape Town, South Africa
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