ICGEB Cape Town Flyer by lanyuehua

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									ICGEB Cape Town
2007-2011
ICGEB




        Trieste   New Delhi Cape Town




                                      The first four years of the ICGEB
                                   Cape Town Component, South Africa
ICGEB Cape Town
                    Trieste   New Delhi Cape Town




ICGEB Cape Town
      2007-2011
        The first four years of the ICGEB
     Cape Town Component, South Africa
ICGEB Cape Town




                  Nippostrongylus brasiliensis.
                  A nematode used to
                  understand the immune
                  response to gastrointestinal
                  worms. This image shows a
                  female worm containing eggs.



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                                                                                      Trieste    New Delhi Cape Town




                                                  Biotechnology
                                                       for Africa
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    for Africa, a vast continent with         All of these are issues that can be
solutions, however, must not be          variegated geography, cultures,           effectively tackled through a science-
restricted to developed countries,       resources, strengths and weaknesses.      based approach focusing on research
but need to be directly implemented      Africa still pays an outrageously high    and its biomedical and agricultural
in developing countries themselves.      death toll to infectious diseases such    applications.
Towards this goal, a serious effort      as malaria (700,000 children under        Capacity building of young African
is required to build human capacities    the age of 5 die every year), or HIV/     scientists on topics of direct relevance
through a global approach, which         AIDS (where every 12 hours, 3,000         to the major health and agricultural
includes training in science and in      people die of this disease). In Africa,   problems of the continent is the
the applications of science, fostering   hunger or malnourishment affect one       ultimate mission of the Cape Town
innovation, building entrepreneurship    third of the population. In addition,     Component of the International
and valuing intellectual property.       non-communicable diseases are             Centre for Genetic Engineering
This is of particular relevance          also increasing at an alarming rate.      and Biotechnology.




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  ICGEB Cape Town




ICGEB Cape Town
The International Centre for Genetic Engineering and Biotechnology
ICGEB, established in 1987, is an        The ICGEB Component laboratories,       on subjects at the forefront of
international, intergovernmental         located in Trieste (Italy), New Delhi   modern biology and biotechnology.
organisation conceived as a Centre       (India) and Cape Town (South            Policy guidelines on the use
of excellence for research and           Africa), provide a scientific and       of ICGEB-owned intellectual property
training with special regard to the      educational environment of the          rights and know-how
needs of the developing world. The       highest international standard.         foster innovative approaches
Centre conducts innovative research      ICGEB offers postgraduate               to industrial relations at a global
in life sciences and strengthens         and postdoctoral fellowships;           level and enhance joint ventures
the research capability of over 60       an international PhD Course is run      for the commercialisation
Member States through training,          in all three ICGEB Components.          of biotechnology research.
funding programmes and advisory          Over 20 practical and theoretical
services.                                courses are organised every year


Why ICGEB
ICGEB is a unique research               Activity is spearheaded by              biotechnology, as well on basic
institution blending high standard       an International Scientific Advisory    research topics.
academic goals, focus on                 Council of top scientists and Nobel     Intellectual property rights generated
developing countries and a mandate       laureates from across the world.        by ICGEB research can be shared
on capacity building.                    Research focuses on issues              by its Member countries; specific
In its three Components, cutting-        of utmost relevance for developing      programmes are in place to directly
edge research is carried out, with       countries, including HIV/AIDS,          transfer technologies to these
scientific excellence as a major goal.   malaria, tuberculosis, plant            countries.




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                                                                                        Trieste   New Delhi Cape Town




The ICGEB Cape Town Component
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.
Currently, the premises of the             infectious diseases (HIV, malaria,        to agricultural biotechnology, will
ICGEB Cape Town Component cover            tuberculosis, trypanosomiasis,            become operational within the next
around 1,200 square metres on the          leishmaniasis and schistosomiasis)        two years.
University of Cape Town, Health            and non communicable diseases             While no single institution can
Science Faculty Campus, and host           (cancer). A Biotech Transfer Unit         tackle the majority of problems
the activity of four Research Groups.      for the development of technologies       and scientific needs of the African
The Component operates research            for biogeneric pharmaceuticals,           continent, ICGEB Cape Town aims
programmes at the forefront of             industrial enzymes and other              to provide a training platform in
scientific excellence, constituting        bio-molecules with potential              topics and techniques that the
the basis upon which the training          industrial applications, has also         trained scientist will later implement
programmes are implemented.                been established. New Research            in disparate fields of research and
Current research focuses on                Groups, including one dedicated           development.


Research and training laboratories         Medicine (IIDMM) of the University        pathogen-free (SPF), viral antibody-
at the ICGEB Cape Town                     of Cape Town. These include               free (VAF) and immunodeficient
Component access state-of-the              resources for cell culture and flow       rodents. Shared equipment and
art instrumentation for advanced           cytometry; advanced optical confocal      resources include facilities for
molecular and cell biology                 microscopy; a BSL-3 safety laboratory     imaging, DNA synthesis, viral vector
applications, and include ICGEB-           for the handling of class-3 pathogens;    production, radioisotope handling,
owned equipment as well as                 a bioexperimentation facility, fully      and access to the Centre for
facilities shared with the Institute for   equipped with survival surgical suites,   Genomics and Proteomics.
Infectious Disease and Molecular           housing for conventional specific


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ICGEB Cape Town




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                                                                                  Trieste   New Delhi Cape Town




                                                                   Personnel
There are approximately 70 people operating at ICGEB Cape
Town, of whom more than 60 are scientists in the laboratories.
Two thirds of these originate from   (the larger the circle, the higher       the University of Cape Town.
African countries, as shown on the   the number of people from that           The pie charts show the division
map above, where the countries       country). Over 20 fellows and            of personnel according to role, level
of origin are indicated as circles   students are funded through              of education, gender and age.


                 ROLe                                            LeVeL OF eDUCATION



                 6%     12%
                              6%
                                      Group Leader                    39%                         Phd
         41%                  12%     Staff Scientist                              24%            University
                                      Post-doc                                                    High School
                                      PhD Student
                      24%             Technician                            37%
                                      Student




                GeNDeR                                                     AGe



                                                                          3% 7%



          48%           52%           Male                        44%               46%           <30
                                      Female                                                      30-40
                                                                                                  40-50
                                                                                                  >50




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  ICGEB Cape Town




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         applications are available on the       framework of its biosafety activities,
programmes offer high-profile,          Web site.                               ICGEB has funded 16, one-year MSc
multidisciplinary training and          Additional activities include student   fellowships in “Risk Assessment
cover a range of topics in genetic      exchange programmes with the            of GM Crops”, dedicated to sub-
engineering and biotechnology.          Royal Society, UK, the National         Saharan African students, at the
The PhD Programme is carried out        Research Foundation, Zaire, the         University of Aberystwyth (UK).
in conjunction with the University of   University of Strathclyde and the       The EU-FP7 funded PRD college
Cape Town.                              University of Glasgow, UK, the          involves collaborative training
African scientists from ICGEB           University of Wuerzburg, Germany        programmes between Cape Town,
Member States are eligible to apply     and the University of Stellenbosch,     Italy, Sweden, Cameroon, Tanzania,
for fellowships. Full details for       South Africa. Furthermore, in the       Uganda, Zambia and Zimbabwe.




African fellows at the ICGEB Components
The ICGEB training programmes           Dean of the Faculty of Agriculture
have funded over 70 African             at the University of Bujumbura
postdocs and PhD students               and is now Liaison Scientist and
since 1989, across 18 African           Coordinator for the International
countries.                              Rice Research Institute (IRRI)
One of its success stories follows      in Burundi.
Dr. Joseph Bigirimana who               The map shows the countries
returned to his native Burundi          of origin of the ICGEB African
in 2007, setting up several rice-       fellows (the larger the spot,
bacterial working models.               the higher the number of people
He has moved on to become the           from that country).




 P|10                            PhD & Postdoc Fellowships: http://www.icgeb.org/fellowships.html
                                                                                     Trieste    New Delhi Cape Town



ICGEB Meetings and Courses in Africa 2007-2011
Every year, the ICGEB organizes          of biomedical research and               ICGEB Member States throughout
over 20 meetings, workshops              biotechnology. Many of these             Africa can apply for financial
and courses in its Components            educational activities are held in       support to organise meetings and
and Affiliated Centres worldwide,        Africa, such as those listed below.      workshops. Criteria for eligibility are
covering subjects at the forefront       Researchers from institutes in           available on the Web site.

 Theoretical Course “Global Infectious Disease Research: a                4-10 September, 2011 - Cape Town,
 multidisciplinary approach”                                              South Africa
 Workshop on “Parasitic Infection and Inflammation”                       23-26 March, 2011 - Cape Town, South Africa
             the ICGEB organizes          and Affiliated Centres worldwide, March 2011 - Pretoria, South these
Every year,Joint Regional Biosafety Workshop “Biosafety of GM Crops:
 Argentina                                                                7-11
                                                                                  biotechnology. Many of Africa
                                          covering subjects at the forefront
over 20 meetings, workshops Affecting Regulatory Decision Making”
 Emerging Issues and Challenges                                                   educational activities are held in
 Joint International Components           of and Southern African                 Africa, - Cape Town, South Africa
and courses in its Conference of the Africanbiomedical research and 6-9 March 2011 such as those listed below.
 Societies of Human Genetics
                                                                          19-22 October, 2010 - Cape Town/Franschhoek,
 Workshop on “African Trypanosomiasis”
                                                                          South Africa
 ICGEB/IUBMB “Genomics and Proteomics Approaches in Cancer                5-11 September, 2010 - Cape Town, South
 Research”                                                                Africa
 Workshop on “Tuberculosis transcriptomics” -                             26-28 June, 2010 - Cape Town, South Africa
Theoretical and Practical Course “Molecular Modelling and Structure-     19-24 April, 2010 - Sfax, Tunisia
Function Relationships Studies of Enzymes of Biotechnology Interest”
Second Advanced Summer School in Africa, Training Course on the          6-14 March, 2010 - Hermanus, South Africa
“Molecular Mechanisms of Viral Infection and Propagation”
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:            14-18 December, 2009 - Ibadan, Nigeria
Protozoan Pathogens Comparative Genomics Workshop”
Theoretical and Practical Course “Fungal Genomics”                       12-18 July, 2009 - Abekouta, Nigeria
Theoretical and Practical Course “Genetic Transformation System          12-17 July, 2009 - Suez, Egypt
in Insects”
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        10-13 December, 2008 - Cape Town,
analyses host/pathogen interactions and inflammatory processes”          South Africa
Workshop on “Risks, benefits and opportunities from the release of       15-19 September 2008 - Cape Town,
GMOs in the African regions”                                             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
                                                                         29 February-9 March 2008 - Cape Town,
The Molecular and Cellular Basis of Infection
                                                                         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   1-8 September, 2007 - Giza, Egypt
of Genetically Engineered Crops (Plants)”
Theoretical and Practical Course “Theoretical and Practical Training     9-13 July, 2007 - Limpopo, South Africa
Workshop in Proteomics and Protein Bioinformatics”
Regional Workshop on “Principles of Biosafety Research for the Release   4-9 February, 2007 - Khartoum, Sudan
of Genetically Engineered Crops”


Meetings & Courses: http://www.icgeb.org/meetings-and-courses.html                                                   P|11
  ICGEB Cape Town




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        fellowships to attend the MSc           conferences, such as the
framework of a 3 million US dollar       course “Managing the Environment”       International Symposium on the
project funded by the Bill & Melinda     at the Aberyswyth University, UK to     Biosafety of Genetically Modified
Gates Foundation to help support         sub-Saharan nationals.                  Organisms (ISBGMO) and the
the development of effective             More than 100 scientists and            Conference of the Parties to the
safety and regulatory systems for        regulators from Sub-Saharan Africa      Convention on Biological Diversity
biotechnology in Africa.                 have been trained at workshops,         Serving as the Meeting of the
Since 2008, ICGEB has granted            while over 30 participants have         Parties to the Cartagena Protocol on
postdoctoral and research                attended regional and international     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 5-9 Sep 2011 - Bobo-Diulasso,
Practical Course for Regulators, Applicants, Reviewers and Inspectors of CFTs 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           7-11 Mar 2011 - Pretoria, South Africa
Decision Making
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 30 Aug-3 Sep 2010 - Accra, Ghana
Practical Course for Regulators, Applicants, Reviewers and Inspectors of CFTs
Theoretical Approaches and their Practical Application in the Risk             22-26 Mar 2010 - Hermanus,
Assessment for the Deliberate Release of Genetically Modified Plants”          South Africa
Introduction to GMO Biosafety Risk Assessment                                  19-23 Oct 2009 - Kampala, Uganda




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                                                                                         Trieste      New Delhi Cape Town




                                                                                       Funding
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.
In addition, funding for research                   Foundation, USA; the Wellcome      Council of South Africa, among
and technology transfer has been                    Trust and the Royal Society, UK;   others. The charts below show the
generated from various external                     the European Commission;           grants obtained from 2007 to April
sources, including the Bill & Melinda               UNESCO; the National Research      2011 and indicate those already
Gates Foundation and the Carnegie                   Foundation and Medical Research    secured up to 2014.

Grants 2007 - 2011
Number of grants                                                                               32

Total amount awarded (Euro)                                                                    3,847,800

Average number of active grants per year                                                       17.6

           N. ACTIVe GRANTS                                    SOURCe OF FUNDING
25                     23
                  21        20
20          18                                                                           Core Budget
 15                               13                                                     External Funds
 10                                                             46%        54%
       6                                 5
 5
                                               1
 0
      07    08    09   10 (11) (12) (13) (14) YEAR

           AMOUNT/1000 (€)
800               779 763
                            705
600         560                   545                           3%                       Government/Public Bodies
                                                                                         Charities/Foundations
400                                                          16%            63%          International Organizations
      236                                                                                Private Companies
200                                     158
                                              101                  19%
 0
      07    08    09   10 (11) (12) (13) (14) YEAR                                                                     P|13
  ICGEB Cape Town




Technology Transfer
ICGEB Collaborations and Technology Transfers across the African Continent
Transfer of technologies is one of the The list below includes Institutes    technologies developed at ICGEB
most relevant activities of ICGEB.     or Companies in Africa to which       have been transferred.

 Centre International de Réference Chantal Biya (CIRCB), Yaounde                                Cameroon
 Institut de Recherche Medicale et d’Etude des Plantes Medicinales (IMPM), Yaounde
 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                                                                        South Africa
 University of Stellenbosch
 South African Pharmaceuticals
 University of Khartoum                                                                         Sudan
 University of Gezira
 Ifakara Health Institute                                                                       Tanzania
 National Institute for Medical Research
 Institute Pasteur                                                                              Tunisia
 Centre of Biotechnology - Sfax
 Makerere University                                                                            Uganda



   Nippostrongylus brasiliensis. Gravid female nematode worms
   surrounded by bubbles with a hooked posterior end and eggs.




 P|14                    Biotechnology Transfer: http://www.icgeb.org/biotechnology-transfer.html
                                                                                         Trieste      New Delhi Cape Town




                                                   Collaborations
                                                            International scientific collaborations
                                                          with the ICGEB Cape Town Component
ICGEB funding is available for research     addressing original scientific questions   launched yearly and full information is
in Africa through its Collaborative Rese-   that show a potential contribution of      available on the Web site. International
arch Programme - a unique source of         particular relevance for the applicant’s   collaborations with the ICGEB Cape
funding aimed at financing projects         country. A call for applications is        Town Component are shown below.


 University of Melbourne                                      Australia
 Ludwig Institute for Cancer Research                         Belgium
 University of Brussels
 Centro Infantil Boldrini, Sao Paulo                          Brazil
 University of Helsinki                                       Finland
 University of Orleans                                        France
 University of Wurzburg                                       Germany
 Forschungszentrum Borstel
 University of Leipzig
 University of Heidelberg
 Technische Universität München
 Heinrich Heine University, Düsseldorf
 University of Pisa                                           Italy
 RIKEN Institute                                              Japan
                                                              New
 University of Wellington
                                                              Zealand
 University of Oslo                                           Norway
 King’s College, London                                       UK
 MRC Mill Hill, London
 University of Strathclyde, Glasgow
 University of Glasgow

 University of Cincinnati, OH                                 USA                  ICGEB Grants to African
 UCSF, San Francisco, CA                                                           Laboratories
 Harvard Medical School and BIDMC Genomics
 Centre, Boston, MA                                                                Since 2007, under the ICGEB Grants
                                                                                   programme, fourteen grants have been
 University of Michigan, MI
                                                                                   awarded to fund projects undertaken in
 University of Rochester, New York, NY
                                                                                   African scientific institutes, for a total of
 Yale University, New Haven, CT                                                    half a million Euro, a number of which
 Virginia Commonwealth University, Richmond, VA                                    co-funded with the Academy of Science
 Massey Cancer Center, Richmond, VA                                                for the Developing World (TWAS).


ICGeB Grants: http://www.icgeb.org/research-grants.html                                                                      P|15
 ICGEB Cape Town




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                                                            Trieste   New Delhi Cape Town




                                                       Publications
Publications 2008-2011
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.
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          2.5
personnel
Total Impact Factor                              332.6
Average Impact Factor per year                   94.8
Average Impact Factor per Publication            5.5




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 ICGEB Cape Town




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                                                                                                      Trieste       New Delhi Cape Town




                                                                                           Research
 Research Group: Cancer Molecular and Cell Biology

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.
Our epidemiological studies                        biopsies. We are investigating the              factors regulating the expression of
focus on the combined effects                      role of HPV in the aetiology of this            the type I collagen genes (one of the
of genetic polymorphisms in the                    cancer and its effects on normal                extracellular matrix proteins).
detoxification genes (cytochrome                   cellular genes.                                 Finally, we developed a series of
p450, glutathione-S-transferases)                  Our interest in tumour cell invasion            ajoene-based analogues that have
and exposure to environmental                      and metastasis centres around the               been shown to be very effective
mutagens and carcinogens to                        degradation and remodelling of                  in killing tumour cells in vitro.
the risk of developing OSSC. The                   the extracellular connective tissue             These analogues will be tested in
Group is performing genome-wide                    proteins. The role of tumour cells              animal models and studies are also
association studies to identify SNPs               in the production of extracellular              underway to investigate the mode of
that confer increased risk to OSCC.                matrix proteins by normal stromal               action of these drugs.
Human Papilloma Virus (HPV) DNA                    fibroblasts is being investigated by            Contact:
has been shown to be present in                    analysing the signal transduction               Iqbal.Parker@icgeb.org
about 40% of South African tumour                  pathways and the transcription

SELECTED PUBLICATIONS                              Africa and Ghana. BMC Genetics 10; 1-5          the role of Sp1 in transcriptional regulation.
Li, D-P., Dandara, C. and Parker, M.I. (2010).     Wang, B, Khachigian, LM, Birrer, MJ, Esau,      Gene, 423, 8-13
Genetic Polymorphisms in the Glutathione           L, Zhou, X. Parker, MI and Hendricks,           Abrahams, A, Mowla, S, Parker, M.I., Goding,
S-Transferase Genes (GSTM1, T1 & P1) and           DT. (2009). A key role for mediating and        C.R. and Prince, S. (2008). UV Mediated
Oesophageal Cancer Susceptibility. BMC             Maintaining GRO/CXCR2 proliferative             Regulation of the Anti-Senescence Factor,
Genetics, 11; 47-56.                               signalling in oesophageal cancer. Mol.          Tbx2. J. Biol. Chem. 283, 2223-2230
Kaschula, C, Hunter, R and Parker, MI              Cancer. Res. 5; 755-764                         Donninger, H, Binder, A, Bohm, L and Parker,
(2010). The anti-cancer activity of ajoene:        Van der Watt PJ, Maske CP, Hendricks DT,        MI. (2008). Differential Effects of Novel Tumour-
the use of chemically synthesised stable           Parker MI, Denny L, Govender D, Birrer          Derived p53 Mutations on the Transformation of
analogues. Biofactors, 36, 78-85                   MJ, Leaner, VD. (2009). The Karyopherin         NIH 3T3 Cells. Biol. Chem, 389, 57-67
Abrahams A, Parker M.I., and Prince S.             proteins, Crm1 and Karyopherin beta1,           Copley, L., van der Watt, P., Wirtz, K.W.,
(2010). The T-box transcription factor Tbx2: Its   are overexpressed in cervical cancer and        Parker, M.I. and Leaner, V.D. (2008).
role in development and possible implication       are critical for cancer cell survival and       Photolon(tm), a chlorin e6 derivative, triggers
in cancer. IUBMB-Life, 62, 92-102                  proliferation. Int J Cancer. 124,1829-1840.     ROS production and light-dependent cell
Torniainen, S., Parker, M.I., Holmberg, V.,        Teng, H., Parker, M.I. and Prince, S. (2008).   death via necrosis. Int. J. Biochem. & Cell
Lahtela, E., Dandara, C. and Jarvela, I. (2009).   Functional characterization of cis-acting       Biol. 40, 227-35
Screening of variants for lactase persistence/     elements involved in basal transcription of
non-persistence in populations from South          the human Tbx2 gene: A new insight into
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   ICGEB Cape Town




Research
Research Group: Cytokines and Disease

Group Leader: Frank Brombacher
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.
Allergic asthma and colitis are                       IL-4/IL-13-activated alternative                    cutaneous leishmaniasis, caused
chosen, non-infectious disease                        macrophages are essential to                        by L. major, activated alternative
models under investigation. Major                     survive acute schistosomiasis due                   macrophages reduced protection
topics include cytokine network                       to downregulation of T helper 1 cell                due to their downregulating influence
regulation; the significance of genes,                responses to avoid hyperinflammation                on protective Th1 responses. The
factors and cells for host protection                 and sepsis. In addition, we                         same cells can cause uncontrolled
are uncovered, supporting our                         demonstrated that IL-4/IL-13-induced                cerebral cryptococcosis and
long-term goal for the development                    smooth muscle cell hypercontractility               influence experimental autoimmune
of safe and cost-effective drug and                   contributes to resistance facilitating              encephalitis.
vaccination strategies.                               expulsion of schisto-eggs as well                   Contact:
Recently, we demonstrated that                        as gut-dwelling helminthes. In                      Frank.Brombacher@icgeb.org

SELECTED PUBLICATIONS                                 protects against gastrointestinal worm infection.   Brombacher. (2008). Interleukin-12p70
Guler R, Afshar M, Arendse B, Parihar SP,             J exp Med. 21:206:2947-57                           Deficiency Increases Survival and Diminishes
Revaz-Breton M, Leitges M, Schwegmann                 Dewals, B., J. C. Hoving, M. Leeto, R. G.           Pathology in Trypanosoma congolense Infection.
A, Brombacher F. (2011) PKC_ regulates                Marillier, U. Govender, A. J. Cutler†, W.           J. Infect. Dis 198:1284-91.
IL-12p40/p70 production by macrophages and            G.C. Horsnell, F. Brombacher. (2009). IL-4R         Barbi, J, F. Brombacher, AR Satoskar. (2008).
dendritic cells, driving a type 1 healer phenotype    responsiveness of non-CD4 T cells contributes       T cells from Leishmania major-susceptible
in cutaneous leishmaniasis. eur J Immunol.            to resistance in Schistosoma mansoni infection      BALB/c mice have a defect in efficiently up-
41:706-15.                                            investigated in pan-T cell-specific IL-4R_-         regulating CXCR3 upon activation. J. Immunol.
Dewals B, Hoving JC, Horsnell WG, Brombacher          deficient mice. J Am Pathol. 175:706-16             181:4613-20
F. (2010). Control of Schistosoma mansoni             FANTOM Consortium. (2009). The                      Magez, S., A. Schwegmann, R. Atkinson, F.
egg-induced inflammation by IL-4-responsive           transcriptional network that controls growth        Claes, M. Drennan, P. De Baetselier, and F.
CD4(+)CD25(-)CD103(+)Foxp3(-) cells is IL-10-         arrest and differentiation in a human myeloid       Brombacher. (2008). The role of B-cells and
dependent. eur J Immunol. 40:2837-47                  leukemia cell line. Nature Genetics 41:553-62       IgM antibodies in paratemia, anemia, and
Herbert DR, Yang JQ, Hogan SP, Groschwitz             Horsnell, W.G., F. Brombacher. (2008) Key           VSG switching in T. brucei-infected mice. PLoS
K, Khodoun M, Munitz A, Orekov T, Perkins             roles for specific and nonspecific antibody         Pathogens, 4:e000122
C, Wang Q, Brombacher F, Urban JF Jr,                 in intestinal nematode expulsion. Cell Host         Schwegmann, A & F. Brombacher. (2008).
Rothenberg ME, Finkelman FD. (2009).                  Microbe 16:303-5                                    Host-directed drug targeting of factors hijacked
Intestinal epithelial cell secretion of RELM-{beta}   Barkhuizen, M., S Magez, B Ryffel and F             by pathogens. Science Signaling 1:29-36.


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                                                                                                Trieste   New Delhi Cape Town




                                                                                     Research
                                           Research Group: Cellular Immunology

Group Leader: Jeffrey Dorfman
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.
Our research interests cover the role                 antibodies”) to successfully inform    Africa. This project will identify
of antibody responses in protection                   vaccine design. To date, most          potential rational drug design targets
against human immunodeficiency                        of the research activity isolating     and identify high priority vaccine
virus (HIV-1) and P. falciparum                       neutralising monoclonal antibodies     targets for both HIV and malaria.
malaria. We focus on three major                      has focused on antibodies from         (3) The development of human
topics within this area. (1) The                      clade B-infected donors, in spite of   monoclonal antibodies against P.
development of human monoclonal                       the fact that approximately half of    falciparum proteins forced to the
antibodies that broadly neutralise                    the HIV infections worldwide are       surface of the infected red blood
various strains of HIV-1. Evidence                    clade C infections including most      cell. Understanding the targets of
supports neutralising antibody                        infections in Southern Africa. (2)     natural immunity to pregnancy-
as an important mechanism for                         Cloning and characterising HIV-1       related malaria in this project will
protection by a future HIV vaccine.                   subtype G envelope genes and their     lead to important vaccine antigen
However, there is not enough                          sensitivity to antibody-mediated       candidates for this disease.
information about the targeting                       neutralisation. This project targets   Contact:
of neutralising antibodies that are                   currently under-studied subtype        Jeffrey.Dorfman@icgeb.org
effective against a broad range of                    G viruses, which infect about 1.5
HIV isolates (“broadly neutralising                   million people, mostly in West
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):1081-4
Oleinikov 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




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  ICGEB Cape Town




Research
Research Group: Cancer Genomics

Group Leader: Luiz Zerbini
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.
We have identified the Cdk11p58,                   against cancer, with less adverse                   that Axl is upregulated in prostate
DEDD and DCN-1 as GADD45-                          reactions. The results so far obtained              cancer and colorectal carcinoma
interacting proteins. Cdk11p58 is a                have established mda-7/IL-24 as a                   cell lines and clinical samples.
Ser/Thr kinase that participates in                crucial mediator of NSAID-induced                   Furthermore, we implicate Axl as
cell cycle progression and is inhibited            apoptosis in cells.                                 a crucial regulator in proliferation,
by GADD45. A second project relates                Another project is the identification               migration, and invasion of prostate
to the elucidation of the molecular                of cell surface receptors in cancer                 cancer cells and tumor formation in
mechanisms of cancer apoptosis                     with particular focus on the tyrosine               vivo. Importantly, we are analysing
induction by structurally different                kinase receptor Axl. Our hypothesis                 a library of natural compounds
Nonsteroidal Anti-Inflammatory Drugs               is that targeting the AXL will inhibit              originating from Africa and Asia with
(NSAIDs). The hypothesis is that                   cancer growth and thus lead to a                    particular focus on Axl inhibition.
NSAIDs and its chemically modified                 novel therapeutic entry point for                   Contact:
versions could act more specifically               cancer. We have demonstrated                        Luiz.Zerbini@icgeb.org
SELECTED PUBLICATIONS                              cell in chronic phase CML is characterized by       Ijiri K, Zerbini LF, Peng H, Out HH, Tsu-
Tsuchimochi K, Otero M, Dragomir C, Plumb          a transcriptional profile resembling normal         chimochi K, Otero M, Dragomir C, Walsh
DA, Zerbini LF, Libermann TA, Komiya S, Ijiri K,   myeloid progenitor cells and reflecting loss of     N, Bierbaum BE, Mattingly D, Flandern G,
Goldring MB. GADD45beta enhances Col10a1           quiescence. Leukemia. 23:892-9. 2009                Komiya S, Aigner T, Libermann TA, Goldring
transcription via the MTK1/Mkk3/p38 axix and       Cho JY, Lee M, Park ES, Ahn JM, Cho JH,             MB A Differential expression of GADD45 in
activation of C/EBP beta-TAD4 in terminally        Lee SJ, Kim BJ, Heo SH, Park HJ, Zerbini LF,        normal and osteoarthritic cartilage: Potential
differentiating chondrocytes. J Biol Chem          Hwang D, and Libermann TA. Proteomic                role in homeostasis of articular chondrocytes.
285(11):8395-407. 2010                             analysis of a PDEF Ets Transcription Factor-        Arthritis and Rheumatism. 58: 2075-2087.
Buffon A, Casali EA Cardoso VV, Zerbini LF,        interacting Protein Complex. J. Proteome Res.       2008.
Robson SC, Sarkis JJ, Wink MR. Differential        8:1327-37. 2009 Konstantinopoulos PA, Fount-        Farinha-Arcieri LE, Carromeu C, Simabuco FM,
expression of nucleotide pyrophosphatase/          zilas H, Zerbini LF, Pillay K, Libermann TA,        Tamura RE, Zerbini LF, Ventura AM. Expression
phosphodiesterases by Walker 256 mammary           Cannistra SA, Spentzos D. Carboplatin-induced       and purification of a recombinant adenovirus
cancer cells in solid tumors and malignant         gene expression changes in vitro are associated     Fiber Knob in a baculovirus system.
ascite. Life Science 86:435-40. 2010               with survival in patients with epithelial ovarian   Intervirology. 51:189-195.2008
Bruns I, Czibere A, Fischer JC, Roels F, Caded-    cancer. BMC Genomics 1:59.2008                      Rücker B, Almeida ME, Libermann TA, Zerbini
du RP, Buest S, Bruennert DHuenerlituerkoglu4,     Dusek JA, Out HH, Wohlhueter AL, Bhasin M,          LF, Wink MR and Sarkis JJ. Kinetic characteriza-
NH Stoecklein AN, Singh R, Zerbini LF, Jager       Zerbini LF, Libermann TA, Benson H. Genomic         tion and molecular identification of the nucleoti-
M, Kobbe G, Gattermann N, Kronenwett R,            Counter-Stress Changes Induced by a Mind            de metabolizing ectoenzymes from rat heart left
Brors B and Haas R The hematopoietic stem          Body Practice. Plos One 3: e2576. 2008.             ventricle. Life Sciences. 82:477-86. 2008.

 P|22
Trieste   New Delhi Cape Town
                 ICGEB Cape Town Component
                 Werner & Beit Building (South), UCT Campus
                 Anzio Road - Observatory 7925
                 Cape Town, South Africa

                 Phone: +27 21 406 6335
                 Fax: +27 21 406 6060
                 E-mail: capetown@icgeb.org

                 www.icgeb.org




International Centre for Genetic Engineering and Biotechnology

								
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