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SANBI was founded in 1996 by Winston Hide, a South African computational biologist who returned from the USA. The Institute has been developed within the University of the Western Cape faculty of Natural Sciences. It is legally part of the UWC. It has a constitution that has been ratified by the Senate of the University. SANBI was founded with funding from the National Research Foundation as a result of the vision of the head of the FRD, Dr. Khotso Mokhele, and had externally funded research from Glaxo and the United States Department of Energy totalling $95 000. The first South African funding that came from outside of the NRF was as a result of a grant from the South African Telecommunnications companies Telkom and later Thintana. In 2000 SANBI submitted a successful proposal for Unit funding from the Medical Research Council and established Africa’s first UWC/SANBI Bioinformatics capacity development unit . The unit has since provided national and international training in a broad spectrum of bioinformatics of pathogens that are widespread in Africa.The Institute has a mission to provide training and development of South Africans in Bioinformatics. The first training officer was hired in 1999. By 2000, SANBI had enrolled 4 PhD students, 2 masters students and had 2 post doctoral researchers. It had already run training modules for hundreds of honours students. SANBI graduated the first PhD in Bioinformatics in Africa in April 2000. In 2003 SANBI became the World Health Organisation Tropical Disease Research programme regional training centre for bioinformatics. Trainees from all over Africa together with faculty at SANBI established the African Society for Bioinformatics and Computational Biology at a meeting at SANBI on 13 February, 2004. In 2003, SANBI became a founding member of the S-star online bioinformatics training alliance.

SANBI led the National genome initiative, hosting the first workshop on genomics in South Africa together with Sydney Brenner in 2000. This initiative contributed to development of the National Biotechnology Strategy. In 2002-3, SANBI expanded the training programme beyond the UWC, by starting up and leading the development of the National Bioinformatics Network. SANBI established a site for the central offices of the NBN at UWC.

SANBI became a member of the European Molecular Biology Network in 1997. It developed close relationships with faculty at the University of Witwatersrand and University of Pretoria, supporting training and research there and at other sites around the country.

Research at SANBI has always been a major focus. In 1997 SANBI published its first article promoting HIV vaccine research and development in Southern Africa in the SA Medical Journal (E. Van der Ryst, C. Gray, C. Williamson, L. Morris, Q. Abdool Karim, W. Hide, J. Esparza. Promoting HIV vaccine research and development in Southern Africa. South African Medical Journal. 1997. Aug;87(8):1015-6.). Its first international publications were in Genome Research (Burke, J., Wang, H., Hide, W. and Davison D. Alternative gene form discovery and candidate gene selection from gene indexing projects. Genome Research., 1998 Mar;8(3):276-90) and the Japanese journal ‘Genome Informatics’ (Hide, W. ,Burke, J., Christoffels, A., Miller, R.. A novel approach towards a comprehensive consensus representation of the expressed human genome. Genome Informatics 1997, pp187-196. Satoru Miyano and Toshihisa Takagi Eds. Universal Academy Press Inc. Tokyo, Japan. ISSN 0919-9454).

SANBI’s first major scientific breakthrough was in collaboration with US investigators and resulted in the discovery of genetic cause for a type of blindness in humans called retinitis pigmentosa (Lori S. Sullivan, John R. Heckenlively, Sara J. Bowne, Jian Zuo, Winston A. Hide, Andreas Gal, Michael Denton, Chris F. Inglehearn, Susan H. Blanton, Stephen P. Daiger. Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa Nature Genetics, 1999 Jul;22(3):255-9). SANBI became the bioinformatics research centre for the Centre for AIDS Programme in South Africa in 2003, and is now integral to HIV research in vaccine development