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International Centre for Genetic Engineering and Biotechnology A centre of excellence for research and training in genetic engineering and biotechnology with special regard to the needs of the developing world. The first six years of the ICGEB Cape Town Component, South Africa ICGEB Cape Town 2007-2013 Developing knowledge Trieste New Delhi Cape Town

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Page 1: 2007-2013 - ICGEB International Centre for Genetic ... · International Centre for Genetic Engineering and Biotechnology A centre of excellence for research and training in genetic

International Centre for Genetic Engineering and BiotechnologyA centre of excellence for research and training in genetic engineering and

biotechnology with special regard to the needs of the developing world.

The first six years of the ICGEB Cape Town Component, South Africa

ICGEB Cape Town2007-2013

Developing knowledgeTrieste New Delhi Cape Town

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ICGEB Cape Town

Page 3: 2007-2013 - ICGEB International Centre for Genetic ... · International Centre for Genetic Engineering and Biotechnology A centre of excellence for research and training in genetic

ICGEB Cape Town2007-2013

The first six years of the ICGEB Cape Town Component, South Africa

Funded by the South African Department of Science and Technology

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Trieste New Delhi Cape Town

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ICGEB Cape Town

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To be effective, such research-driven solutions, however, must not be restricted to developed countries, and need to be directly implemented in developing countries. Towards this goal, a serious effort is required to build human capacities through a global approach, that 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 diverse geography, cultures, resources, strengths and weaknesses. Africa still has an outrageously high death toll due to infectious diseases such as malaria and HIV/AIDS. In Africa, hunger or malnourishment affect one third of the population. In addition, non-communicable diseases such as obesity, diabetes and cancer are increasing at an alarming rate. All of these are problems

that can be effectively tackled through a sciencebased 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 needs of the continent is the ultimate mission of the Cape Town Component of the International Centre for Genetic Engineering and Biotechnology.

There is increasing international recognition that science- and technology-intensive solutions can significantly improve the quality of life of our citizens. This is particularly true where biotechnology is concerned, a field that is of paramount interest in 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).

Biotechnology for Africa

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ICGEB Cape TownThe International Centre for Genetic Engineering and Biotechnology

Why ICGEB

ICGEB, established in 1987, is an international, intergovernmental organisation conceived as a Centre of excellence for research and training with special emphasis on the needs of the developing world. The Centre conducts innovative research in life sciences and strengthens the research capability of over 63 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.

The ICGEB is a unique research institution that blends 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 monitored by an International Scientific Advisory Council of prominent 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 as 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.

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 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 Gates Foundation Millennium Development Goals.

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,

The ICGEB Cape Town Component

Iqbal ParkerDirector of Component

ICGEB Cape Town

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ICGEB Membership in Africa 2008-2013

Research and training laboratories at the ICGEB Cape Town Component have access to 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 (IDM) 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, housing for conventional specific

pathogen-free (SPF) animals, 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.

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 few 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.

Mauritius

Ethiopia

Côte d’Ivoire

Liberia

Senegal

TunisiaMorocco

Kenya

Tanzania

Mauritania

AlgeriaEgypt

Sudan

Nigeria

SouthAfrica

Dem.Republicof theCongoCongo

BeninGhana

Burkina Faso

Mauritius

CameroonEthiopia

Côte d’Ivoire

Liberia

Senegal

TunisiaMorocco

Kenya

Tanzania

Angola

Namibia

Mauritania

AlgeriaEgyptLibya

Sudan

Nigeria

SouthAfrica

Dem.Republicof theCongo

Lesotho

Congo

BeninGhana

Burkina Faso

Membership States

Signatory Countries

2008 2013

Trieste New Delhi Cape Town

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ICGEB Cape Town

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The ICGEB Cape Town has a staff complement of 70 people, of whom more than 60 are scientists in the laboratories.

Statistics for 2012 - 2013

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

from external sources.The pie charts show the division of personnel according to role, gender and age.

Personnel

40+60+K 35+53+9+3+KMaleFemale

6+4+16+25+5+19+12+3+10+M Group LeaderStaff ScientistPostdoctoral FellowPhD StudentTechnicianStudentVisiting StudentsVisiting ScientistsAdministration

<3030-4040-50>50

Role

Gender Age

25%

16%

4%6%10%

3%

12%

19%

5%

40%

60%

53%

35%

9%3%

9

Trieste New Delhi Cape Town

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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.

African fellows at the ICGEB Components

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 and the application procedure are available on the website. Additional activities include

student exchange programmes with the Royal Society, UK, the National Research Foundation, Democratic Republic of the Congo, the University of Strathclyde and the University of Glasgow, UK, the University of Wuerzburg, Germany, Al-Farabi Kazakh National University, Kazakhstan, University of Nsukka, Nigeria, Instituto do Caracao, FK Biotec and Ludwig Institute, Brazil 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 Poverty Related Diseases college involves collaborative training programmes between South Africa, Italy, Sweden, Cameroon, Tanzania, Uganda, Zambia and Zimbabwe.

Training

The ICGEB training programmes have funded over 80 African postdocs and PhD students since 1989, across 18 African countries.

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).

PhD & Postdoc Fellowships: http://www.icgeb.org/fellowships.html

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ICGEB Cape Town

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Fellowships awarded: Postdoctoral2008-2013

Fellowships awarded: PhD & Masters2008-2013

0

14

12

6

8

10

4

2

0

14

18

16

20

12

6

8

10

4

2

Cancer Genomics

Cancer Genomics

Cancer Molecular and Cell Biology

Cancer Molecular and Cell Biology

Cellular Immunology

Cellular Immunology

Cytokines and Disease

Cytokines and Disease

Biosafety Unit (*Research Fellows)

Num

ber

of

Pos

tdoc

sN

umber

of

Stu

den

ts

Research Group / Unit

Research Group

ICGEBExternal

ICGEBExternal

11

Trieste New Delhi Cape Town

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0

14

16

12

6

8

10

4

2

Cancer Genomics

Num

ber

of

Gra

dua

tes

Research Group

Cancer Molecular and Cell Biology

Cellular Immunology

Cytokines and Disease

ICGEBExternal

Graduated: PhD and Masters2008-2013

Origin of all Fellows: 2008-2013

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ICGEB Cape Town

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ICGEB Meetings and Courses in Africa 2007-2013Every year, the ICGEB organisesover 20 meetings, workshopsand courses both at its Componentsand Affiliated Centres worldwide,covering subjects at the forefront

of biomedical research andbiotechnology. Many of theseeducational activities are held inAfrica, such as those listed below.Researchers from institutes in

ICGEB Member States throughoutAfrica can apply for financialsupport to organise meetings andworkshops. Criteria for eligibility areavailable on the website.

Course on “Global Infectious Diseases Research: A Multidisciplinary Approach” 6-13 October, 2013 – Cape Town, South Africa

Course on “Non communicable Diseases in Developing Countries” 15-19 October, 2012 – Cape Town, South Africa

ICGEB/IUBMB Summer School on “Nutrition and Disease: Biochemical and Molecular Insights” 24-31 March, 2012 – Cape Town, South Africa

Course on “Global Infectious Diseases 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 AfricanSocieties 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 visualise and analyse 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

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Trieste New Delhi Cape Town

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The generous contribution from the Government of South Africa,through the Department of Science and Technology, and the initial 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.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. The charts show the grants obtained between 2008 to 2013.

Funding

Grants 2008 - 2013Number of grants: 44

Total amount awarded: € 4,883.486

Average number of active grants per year: 19.6

300=

350=

380=

370=

305=

220=

0

25

15

20

10

5

08 09 10 11 12 13

18 21 23 22 19 15

280=

380=

369=

500=

479=

407=

0

1200

600

800

1000

400

200

08 09 10 11 12 13

560 779 763 1000 959 814

Number of Active Grants

Year

Amount / 1000€

Year

14

ICGEB Cape Town

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58+42+KSource of Funding

Official visit of South African Minister of Science and Technology, Mr Derek Hanekom, MP to the Cape Town Component, 29 May 2013

58%

42% 66+14+17+3+KCore BudgetExternal Funds

Government/Public BodiesCharities/FoundationsInternational OrganisationsPrivate Companies

14%

66%

3%

17%

Trieste New Delhi Cape Town

15

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ICGEB Technology Transfers across the African Continent

Transfer of technologies is one of the most relevant activities of the ICGEB. The list below includes Institutes or Companies in Africa to which technologies developed at ICGEB have been transferred.

Technology TransferBiotechnology Transfer: http://www.icgeb.org/biotechnology-transfer.html

EIPICO - Egyptian International Pharmaceutical Industries CO Egypt

University of Maiduguri Teaching Hospital Nigeria

South African Pharmaceuticals South Africa

Institute PasteurCentre of Biotechnology - Sfax

Tunisia

ICGEB Cape Town

16

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International scientific collaborations with the ICGEB Cape Town ComponentICGEB funding is available for research in Africa through its Collaborative Research 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 annually and

full information is available on the website. International collaborations with the ICGEB Cape Town Component are shown below.

Collaborations

ICGEB Grants to African LaboratoriesSince 2007, under the ICGEB Grants programme, 20 grants have been awarded to fund projects undertaken in African scientific institutes, totalling more than half a million Euro, a number of which are co-funded with the The World Academy of Science (TWAS) for the Developing World.

Queenstown University of Technology; University of Melbourne Australia

Ludwig Institute for Cancer Research; University of Brussels Belgium

Centro Infantil Boldrini, Sao Paulo; PUC Rio Grande do Sul; UFRGS Brazil

Centre International de Réference Chantal; Biya (CIRCB), Yaounde; Institut de Recherche Medicale et d’Etude des Plantes Medicinales (IMPM), Yaounde

Cameroon

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; University of Rome Tor Vergata and National Research Council (CNR), Rome Italy

RIKEN Institute Japan

Al-Farabi Kazakh National University Kazakhstan

Kenya Medical Research Institute (KEMRI); University of Nairobi Kenya

Centro de Investigação em Saúde de Manhiça Mozambique

University of Wellington New Zealand

University of Oslo Norway

University of Khartoum; University of Gezira Sudan

University of Bern Switzerland

Ifakara Health Institute; National Institute for Medical Research Tanzania

Makerere University Uganda

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

http://www.icgeb.org/research-grants.html

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ICGEB Cape Town

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Publications 2008-2013

ICGEB publishes results from its research in high Impact Factor, international peer-reviewed scientific journals. The statistics below show the number of publications authored to date by scientists from the ICGEB Cape Town Component.

Publications

Total number of scientific publications 119

Number of publications with Impact Factor ≥ 6 38

Average number of publications per year 19.8

Number of publications per researcher 3.6

Total Impact Factor 697.9

Average Impact Factor per year 116.3

Average Impact Factor per Publication 5.9

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Trieste New Delhi Cape Town

Page 20: 2007-2013 - ICGEB International Centre for Genetic ... · International Centre for Genetic Engineering and Biotechnology A centre of excellence for research and training in genetic

Group Leader: Iqbal Parker

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.

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. Since viral sequences such as HPV and EBV have been shown to be present in OSCC biopsies, we have sequenced the entire genomes of some of our patients and are

currently analysing the DNA sequence data for large insertions and deletions. The insertions will be screened for possible remnants of viral genomes. 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:

[email protected]

SELECTED PUBLICATIONSWang, 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; 755-764Kaschula, C, Hunter, R and Parker, MI (2010). The anti-cancer activity of ajoene: the use of chemically synthesised stable analogues. Biofactors, 36, 78 - 85Bye, H, Prescott, N.J, Matejcic, M, Lewis, C.M, Parker, M.I, and Mathew, C.G. (2011). Population-specific genetic associations with oesophageal squamous cell carcinoma in South Africa. Carcinogenesis, 32, 1855 - 1861Matejcic, M, Li, D-P, Prescott, N.J, Lewis, C.M, Mathew C.G, and Parker, M.I. (2011). Association of a deletion of GSTT2B with an altered risk of oesophageal squamous cell carcinoma in a

South African population: A case-control study. PLosONE, e29366. Epub 2011 Dec 27Dzobo, K. Leaner V.D. and Parker, M.I. (2012) Feedback Regulation of the α 2(1) Collagen Gene via the MEK-ERK Signalling Pathway. IUBMB-Life, 64, 87 - 98.Vogelsang, M, Wang, Y, Veber, N, Mwapagha, L and Parker, M.I. (2012). The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk. PLosONE, e36962, Epub May, 2012.Bye,H., Prescott, N.J., Lewis, C.M., Matejcic, M., Moodley. L., Robertson, B., van Rensburg, C., Parker, M.I. and Mathew, C.G. Distinct genetic association at the PLCE1 locus with oesophageal squamous cell carcinoma in the South African population. Carcinogenesis 2012 Aug 3. [Epub] PMID:22865593. Schäfer, G., Kabanda, S., van Rooyen, B., Marušič,

M.B, Banks, L. Parker, M.I. (2013) The Role of Inflammation in HPV Infection of the Oesophagus, BMC Cancer 13, 185 - 194 (PMID:23570247).Paccez, J.D., Vogelsang, M., Parker, M.I. and Zerbini, L.F (2013). The receptor tyrosine kinase Axl in cancer: biological functions and therapeutic implications. Int J Cancer, doi: 10.1002/ijc.28246. [Epub] PMID:23649974).Wang, Y., Vogelsang, M., Schäfer, G., Matejcic, M., Parker, M. I. (2013). MicroRNA polymorphisms and environmental smoke exposure as risk factors for oesophageal squamous cell carcinoma. PLosONE 13; 10 e78520 Epub October 2013.van Rooyen, B., Schäfer, G., Leaner, V.D. and Parker, M.I. (2013). Tumour cells down-regulate CCN2 gene expression in co-cultured fibroblasts in a Smad7- and ERK-dependent manner. Cell Commun Signal. 11:75. [Epub] PMID:24090133.

Research

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Page 21: 2007-2013 - ICGEB International Centre for Genetic ... · International Centre for Genetic Engineering and Biotechnology A centre of excellence for research and training in genetic

Research

Group Leader: Frank Brombacher

Our research interest is the immunological mechanisms of host protection in infectious and non-infectious diseases. The Group investigates immunological mechanisms in experimental murine models for human diseases. Major general topics include cytokine network and regulation, lymphocyte differentiation and function, dendritic cell and macrophage activation, as well as the role of non-immunological effector cells in health/disease like smooth muscle cells, goblet cells, activated by IL-4 and IL13.

Research Group: Cytokines and Disease

Current disease models under investigations include: Bacterial Infectious Diseases:Tuberculosis and Listeriosis, Parasitic Infectious Diseases: African trypanosomiasis, Cutaneous leishmaniasis, Schistosomiasis (Bilharzia) and Hookworm. Non-infectious Diseases: Allergic inflammation and Colitis. Our research strategy is based on gain

of knowledge by a loss of function approaches in knockout and knockdown animal models. This includes the generation and characterisation of novel conditional gene deficient mouse strains. Together with transcriptomic approaches, the significance of genes, factors and cells for host protection and failure thereof are uncovered and possible factors for

host-directed drug targeting identified. This supports our long-term goal for the development of safe and cost-effective drug and vaccination strategies.

Contact:

[email protected]

SELECTED PUBLICATIONSNdlovu, H., M. Darby, M. Froelich, W. Horsnell, F. Lühder T. Hünig and F Brombacher. 2013. CD28 costimulation is required for T follicular helper cell expansion and type-2 mediated N. brasiliensis immunity during secondary infection. PLOSpathogen in press.Hurdayal, R., N.E. Nieuwenhuizen, M. Revaz-Breton, L. Smith1, J.C. Hoving, S.P. Parihar, B.Reizis and F.Brombacher. 2013. Deletion of IL-4 receptor alpha on dendritic cells renders BALB/c mice hypersusceptible to Leishmania major infection. PLOSpathogen 9:e1003699Horsnell, WGC, M Darby, JC Hoving, N Nieuwenhuizen, S Bobat, H Ndlovu, M Kimberg, F Kirstein, AJ Cutler, B DeWals, AF Cunningham and F Brombacher. 2013. Rapid IL-4R<alpha> associated antigen processing by B cells promotes recall immunity in Nippostrongylus brasiliensis infection. PLOSpathogen 9:e1003662Zeng MY, Pham D, Bagaitkar J, Liu J, Otero K, Shan

M, Wynn TA, Brombacher F, Brutkiewicz RR, Kaplan MH, Dinauer MC. 2013. An efferocytosis-induced, IL-4-dependent macrophage-iNKT cell circuit suppresses sterile inflammation and is defective in murine CGD. Blood. 121:13487-93Thawer SG, Horsnell WG, Darby M, Hoving JC, Dewals B, Cutler AJ, Lang D, Brombacher F. 2013. Lung-resident CD4+ T cells are sufficient for IL-4Rα-dependent recall immunity to Nippostrongylus brasiliensis infection. Mucosal Immunol. 2013 Jun 19. doi: 10.1038/mi.2013.40. [Epub ahead of print]Parihar, SP, Guler, R, Lang, DM, Khutlang, R, Mhlanga, MM, Suzuki, H, Marais AD and Brombacher F. 2013. Statins mediate protection against Mycobacterium tuberculosis infection by enhancing phagosomal maturation and autophagy. J. Inf. Dis. Oct 16. [Epub ahead of print]Jenkins SJ, Ruckerl D, Thomas GD, Hewitson JP, Duncan S, Brombacher F, Maizels RM, Hume DA, Allen JE. 2013. IL-4 directly signals tissue-resident

macrophages to proliferate beyond homeostatic levels controlled by CSF-1. 2013. J Exp Med. 2013, 210:2477-91Nieuwenhuizen NE, Kirstein F, Jayakumar J, Emedi B, Hurdayal R, Horsnell W, Brombacher F 2012. Allergic airway disease is unaffected by the absence of IL-4Ra-dependent alternatively activated macrophages. J Allergy Clin Immunol, 130:743-50 Hoving, JC, F. Kirstein, N. Nieuwenhuizen, E. Hobeika, M. Reth and F. Brombacher 2012. Immunoglobulin E-producing B lymphocytes mediate colitis in BALB/c mice. Gastroenterology, 142:96-108. Strasser D, Neumann K, Bergmann H, Marakalala MJ, Guler R, Rojowska A, Hopfner KP, Brombacher F, Urlaub H, Baier G, Brown GD, Leitges M, Ruland J. 2012 Syk Kinase-Coupled C-type Lectin Receptors Engage Protein Kinase C-δ to Elicit Card9 Adaptor-Mediated Innate Immunity. Immunity. 36:32-42

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Group Leader: Jeffrey Dorfman

Effective vaccines will be among of the best hopes for controlling the global HIV and malaria epidemics, and making effective vaccines will require a better understanding of the interplay with the immune system.

Research Group: Cellular Immunology

Our research focuses on two important potential vaccine targets: the Membrane Proximal External Region (MPER) of the gp41 subunit of HIV Envelope and the PG9/PG16 site in the gp120 subunit: We have evidence that suggest that some HIV-1 isolates are able to shield the MPER from many antibodies. This would mean that only the limited proportion of anti-MPER antibodies that can penetrate this obstruction would be able to provide the protection against the large number of HIV-1 variants that would be desirable in a vaccine. We are now focusing upon the mechanism. Other projects focus upon which conformation of envelope is targeted by the antibodies that target the PG9/PG16 site and upon the

envelopes of the understudied but greatly important subtype G.Unlike many pathogens, P. falciparum malaria can readily infect the same person repeatedly. Years of exposure induce development of “functional” immunity that prevents significant disease, often without eradicating infection. Thus, people sometimes harbour chronic, asymptomatic infections for long periods of time that sometimes break out and cause disease. Control of recrudescence can be best studied in a mouse model partly because we can control re-exposure. Past evidence suggests that the immune response needed to control recrudescent infections is different from the immune response needed to control acute

infections. It is widely thought that control of recrudescent Plasmodium chabaudi infections in mice requires a switch from a Th1-type to a Th2-type immune response. We are following up on recent evidence that this Th1 to Th2 switch may not be the key, but that IL-4 responsiveness of a non-T cell may be critical. Other key projects in the lab focus upon the immunogenicity of candidate vaccine antigens in malaria endemic areas (with ICGEB New Delhi) and upon control of transcription in P. falciparum (with the Zerbini laboratory – ICGEB Cape Town).

Contact:

[email protected]

SELECTED PUBLICATIONJacob RA, Abrahams F, Tongo M, Schomaker M, Roux P, Mpoudi Ngole, E, Burgers WA, Dorfman JR. (2012) Refined identification of neutralization-resistant HIV-1 CRF02_AG viruses. J Virol: 86(14):7699-7703

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ICGEB Cape Town

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Group Leader: Luiz Zerbini

The overall goals of the Group are to utilise genomics and proteomics tools and signal transduction resources to accelerate comparative analysis of aberrant gene expression in carcinogenesis and to study alterations in signal transduction pathways during development of cancers.

Research Group: Cancer Genomics

The group is concerned with deciphering the molecular mechanisms of action of the GADD45 family of genes and their protein partners. GADD45 plays an unambiguous role in the ability of tumors to escape programmed cell death. The goal of these studies is to identify new molecular targets for cancer treatment using genomics and proteomics platforms. The 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 NSAIDs and its chemically modified versions could act more specific against cancer, with less adverse reactions. The third project is focused on identification

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.The fourth project intends to develop a platform to design safer, less toxic and more target-specific drugs for cancer therapy. We will conduct computational ligand-based virtual screening of databases using identified compounds as ligands to identify related drug-like commercially available analogues for purchase and anti-tumour screening. The fifth project will analyse the genetic basis of prostate cancer development in the African population. Here, again, we will perform large scale genomics and proteomics

research in order to identify genes involved in the progression to a more aggressive stage of the disease that is prevalent in the African population. The sixth project is based on understanding the role of cell-competition in the mechanism of cancer initiation, proliferation and tumor-therapy. This proposal aims to understand the role of cell-competition and Flower code in tumor growth and proliferation. In addition the project proposed high clinical significance since Flower code can have the potential to function as a universal bio-marker for more than one type of cancer.

Contact: [email protected]

SELECTED PUBLICATIONSPaccez JD, Vogelsang M, Parker MI and Zerbini LF. The receptor tyrosine kinase Axl in cancer: biological functions and therapeutic implications. International Journal of Cancer. 134: 1024-33. 2014 Paccez JD, Vasques GJ, Bhasin M, Correa RG, Vasconcellos JF, Gu X, Libermann TL and Zerbini LF. The tyrosine receptor kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth. Oncogene. 32:689-98s. 2013Li J, Weinberg MS, Zerbini LF and Prince S. The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signalling pathway. Molecular Biology of the Cell. 24:3569-76. 2013Silva HB, Amaral EP, Nolasco E, Victo NC, Atique R, Jank C, Anschau V, Zerbini LF, Correa RG.

Dissecting major signaling pathways throughout the development of prostate cancer. Prostate Cancer 2013:920612. 2013Duncan K, Schäfer G, Vava A, Parker MI and Zerbini LF. Targeting neddylation in cancer therapy. Review. Future Oncology 8: 1461-70. 2012Duncan K, Uwimpuhwe H, Czibere A, Sarkar D, Libermann TA, Fisher PB and Zerbini LF. NSAIDs induce apoptosis in non-proliferating ovarian cancer cells and inhibit tumor growth in vivo. IUBMB Life 64(7):636-43. 2012Tamura RE, de Vasconcellos JF, Sarkar D, Libermann TA, Fisher PB and Zerbini LF. GADD45 proteins: central players in tumorigenesis. Review. Current Molecular Medicine 12(5):634-51. 2012Zerbini LF, Tamura RE, Correa RG, Czibere A, Cordeiro J, Bhasin M, Simabuco FM, Wang Y, Gu X,

Li L, Sarkar D, Zhou JR, Fisher PB and Libermann TA. Combinatorial effect of Non-Steroidal Anti-inflammatory Drugs and NF-κB inhibitors in ovarian cancer therapy. Plos One 6:e24285. 2011Bruns I, Czibere A, Fischer JC, Roels F, Cadeddu RP, Buest S, Bruennert DHuenerlituerkoglu, 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. 2009Cho 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. Journal of Proteome Research. 8:1327-37. 2009

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Trieste New Delhi Cape Town

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The Biosafety Unit, in partnership with the Bill & Melinda Gates Foundation, is implementing a Project focusing on enhancing the ability of regulatory authorities in sub-Saharan Africa (SSA) to regulate the development and/or commercialisation of the products of modern agro-biotechnology (genetically modified [GM] products). This is being achieved through the development of a pool of African expertise by which biosafety regulatory systems can be staffed effectively and sustainably, as well as provision of in-country assistance in improving regulatory effectiveness.

The first phase (2009-2012) of the project focused on: i) enhancing local knowledge in biosafety, through the completion of 8 training workshops in which 214 Africans participated, and by supporting 39 delegates to 9 international meetings, and; ii) integrating biosafety research results into national/regional biosafety regulatory frameworks, by supporting the completion of a MSc programme in GM crop risk assessment by 16 African regulators and technical advisors. The current second phase (2013-2016) is geared towards expanding and building

upon the first phase and involves: i) the provision of advanced academic training in biosafety; ii) the re-integration of personnel academically-trained during the project into their national biosafety regulatory systems; iii) organising biosafety training workshops tailored to local and regional needs, and; iv) offering a limited number of regulatory exchange opportunities to African regulators and their scientific experts to visit established regulatory offices currently processing applications for import, confined and commercial releases of GM products, and vice versa,

to experienced non-African regulators to visit a limited number of regulatory offices in SSA to provide local assistance in improving regulatory effectiveness. In acknowledgement of the numerous on-going biosafety programmes currently operating in SSA, efforts are being made to enhance partnerships with, and add value, to these programmes.

Contact: [email protected] and

[email protected]

Biosafety UnitProgramme Officer: Dennis Ndolo Obonyo

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ICGEB Cape Town

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ICGEB Biosafety Courses & Workshops in Africa, 2009-2013Workshop on Problem formulation in Biosafety Risk Analysis 30 September - 4 October, 2013 - Accra, Ghana

Regulatory consultation: Providing support to Ghanaian regulatory authorities aimed at developing and implementing enduring regulatory procedures, while ensuring compliance with national legislative requirements

26 August - 27 September, 2013 - Accra, Ghana

Workshop on Integrating problem formulation into the process of risk analysis of GMOs 10-14 June, 2013 - Dar es Salaam, Tanzania

A Discussion of the Key Elements in GMO Regulation December, 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 September, 2011 - Bobo-Diulasso, Burkina Faso

Stakeholder Workshop on Biosafety Risk Communication 8-10 June, 2011 - Quatre Bornes, Mauritius

South Africa/Argentina Joint Regional Biosafety Workshop and Seminar on Biosafety of GM Crops: Emerging Issues and Challenges in Regulatory Decision Making

7-11 March, 2011 - Pretoria, South Africa

Workshop on Risk Analysis for the General Release of Genetically Modified Crops 14-18 December, 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 August - 3 September, 2010 - Accra, Ghana

Workshop on Theoretical Approaches and their Practical Application in the Risk Assessment for the Deliberate Release of Genetically Modified Plants

22-26 March, 2010 - Hermanus, South Africa

Workshop on Introduction to GMO Biosafety Risk Assessment 19-23 October, 2009 - Kampala, Uganda

SELECTED PUBLICATIONSRacovita M, Obonyo D.N, Craig W and Ripandelli D (2014) What are the non-food impacts of GM crop cultivation on farmers’ health? Environmental Evidence, 3:1 Racovita M, Obonyo DN, Abdallah R, Anguzu R,

Bamwenda G, Kiggundu A, Maganga H, Muchiri N, Nzeduru C, Otadoh J, Rumjaun A, Suleiman I, Sunil M, Tepfer M, Timpo S, van der Walt W, Kaboré-Zoungrana C, Nfor L, & Craig W. (2013). Experiences in sub-Saharan Africa with GM crop risk communication: outcome of a workshop.

GM Crops and Food 4(1), 19-27. Obonyo DN, Nfor LM, Uzochukwu S, Araya-Quesada M, Farolfi F, Ripandelli D, & Craig W. (2011). Identified gaps in biosafety knowledge and expertise in sub-Saharan Africa. AgBioForum, 14(2), 71-82.

1. A working group session during the ICGEB workshop, Problem Formulation in Biosafety Risk Analysis, 30 September- 4 October 2013 Accra, Ghana. 2. Dr. Dennis N. Obonyo and Dr. Paul Keese at a cowpea Confined Field Trial Site in Tamale, Ghana during an in-country working partnership (26 August - 27 September 2013) with Ghanaian regulatory authorities. 3. Participants at ICGEB workshop, Problem Formulation in Biosafety Risk Analysis, 30 September – 4 October 2013 Accra, Ghana 4. The ICGEB funded students undertaking the 2013-2014 Master Programme in Plant Biotechnology at the School of Food and Wine of The University of Adelaide, Australia. 5. A visit to the Mikocheni Agricultural Research Institute as part of the ICGEB workshop, Integrating Problem Formulation in the Process of Risk Analysis of GMOs, 10-14 June 2013, Kunduchi Hotel, Dar es Salaam, Tanzania 6. A section of participants at the kick off meeting for the second phase of the ICGEB Biosafety capacity Building Project

for SSA 28 February-1 March 2013, ICGEB Cape Town

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ICGEB Cape Town

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ICGEB Cape Town ComponentWernher & Beit Building (South)

UCT Campus, Anzio Road - Observatory 7925Cape Town, South Africa

Phone: +27 21 406 6335Fax: +27 21 406 6060

Email: [email protected]

www.icgeb.org

February 2014

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International Centre for Genetic Engineering and Biotechnology

ICGEB Cape Town ComponentWernher & Beit Building (South)UCT Campus, Anzio Road - Observatory 7925Cape Town, South Africa

Phone: +27 21 406 6335Fax: +27 21 406 6060Email: [email protected]

www.icgeb.org