Research
Vaccinology / protein expression:
Research activities are centred on the use of plants and of recombinant baculoviruses in insect tissue cultures to make candidate vaccines against Human papillomavirus types 16 and 11, HIV-1 subtype C, Beak and feather disease virus (BFDV) of psittacines, and H5N1 influenza virus. The group also has a strong interest in the use of novel DNA vaccine vectors incorporating Porcine circovirus type 1 (PCV-1) enhancer elements, and of lambda phage-derived encapsidated DNA vaccines.
The vaccine development activities were originally initiated as a result of a perception of an almost complete lack of activity in this area in this country, and especially for human papillomavirus (HPV), which causes cervical cancer. This is presently the worst cancer in women in South Africa as in the rest of the developing world, and is entirely preventable. These efforts, begun in collaboration with Prof Anna-Lise Williamson of UCT, were soon expanded into work on HIV-1 subtype C vaccines under the auspices of the SA AIDS Vaccine Initiative (SAAVI), so that I became part of a broad consortium of some 50+ researchers at UCT and elsewhere working on cheap, novel vaccines against sexually transmitted diseases affecting mainly poor people.
Plant expression activities include very successful transient and transgenic expression of papillomavirus proteins, HIV-1C Gag derivatives, H5N1 influenza HA protein, and chicken antibody short-chain variable region antibodies.
After two successive Innovation Fund grants we have two candidate HPV vaccines awaiting further development and possibly human trial, and our HIV vaccine work is in its third 3-year funding cycle with the emphasis on production of polyprotein virus-like particles in insect cells. The parrot vaccine project grew out of the expertise base established for the other projects, is well advanced, and is in its second funding cycle. We are finalizing an application to PlantBio (SA Government-funded biotechnology seed funder) for exploration of new technologies for high-level plant expression of foreign genes, and for the large-scale expression of commercially important proteins in plants.
Advanced technologies presently established in my group include the use of recombinant baculoviruses to express foreign proteins, and the use of plants for high-level transgenic and transient expression of foreign proteins. We have significant capability for the purification of proteins from cell cultures or plants, including high-throughput column technologies and flow-through centrifugation, as well as sophisticated plant growth facilities and access to large-scale bioreactors (10 – 20 litres).
Molecular virology / general plant biotechnology:
These activities include a continuing investigation of geminivirus diversity and molecular biology (since 1985), engineering resistance in maize to maize streak virus, and in investigating the genetic diversity of beak and feather disease virus of psittacines in southern Africa. I also have an interest in the use of geminiviruses as vectors of foreign genes in plants.
The plant pathology history and the plant engineering activities have always been aimed at understanding diseases of staple food crops of people in Africa, and eventually at controlling them. Success in this regard has come recently, with the successful culmination of a 20-year project on maize streak virus: our group has, in collaboration with Prof Jennifer Thomson, succeeded in engineering transgenic resistance to the virus into maize. This is of tremendous potential benefit to small farmers in the whole of Africa, where the virus is the second worst pathogen affecting the crop, given that it will allow the rapid generation of suitable resistant varieties suited to many different climatic and agronomic niches, and dramatic improvements in crop yields. Other activities involving the collaborative engineering of multiple resistances into maize and other crops, and the establishment of novel expression systems in plants are in train, with multiple South African collaborators.
[ For more detail on research activities go to this page ]
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A colorised geminivirus particle: 18 x 30 nm, single coat protein, containing a single molecule of circular single-stranded DNA |
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A virus-like particle made from Human papillomavirus (HPV) type 16 L1 major capsid protein expressed in Sf21 insect cells via recombinant baculovirus (70 nm) |
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A virus-like particle made from Human immunodeficiency virus (HIV) type 1 subtype C Pr55 Gag protein, budded out of Sf21 cells (~100 nm) |
Funding:
| Grant | Co-Investigators |
|---|---|
| DACST Innovation Fund PROJECT No 41224 2000 - 2002 | A-L Williamson, B Ryffel, T Tucker, C Albrecht (CANSA) |
| DACST Innovation Fund 4th Round 2003 - 2005 | M O’Kennedy (CSIR), JT Burger (Stell), K Kunert (UP) |
| Unlocking the Future 2004-2006 | Dionne Shepherd |
| NRF Focus Area Grant: Unlocking the Future 2007-2009 | Dionne Shepherd |
| NRF Focus Area Grant: EGIC 2004-2006 | Rob Bragg (UFS), A-L Williamson |
| NRF Focus Area Grant: EGIC 2007-2009 | Rob Bragg (UFS), A-L Williamson, Livio Heath (ARC-OVI) |
| NRF Focus Area Grant: EGIC 2007-2009 | A-L Williamson, E Shephard, C Williamson |
| SA AIDS Vaccine Initiative (SAAVI) 2000 - 2002 | A-L Williamson, E Shephard, C Williamson |
| SAAVI 2003-2005 | A-L Williamson, E Shephard, R Chikwamba (CSIR) |
| SAAVI 2006-2008 | A-L Williamson, I Hitzeroth |
| PRF Major Impact Project 2002 - 2004 | A-L Williamson, I Hitzeroth |
| PRF Grant 2005-2008 | A-L Williamson, J Maclean |
| PRF Extraordinary Grant 2006-2007 | A-L Williamson, I Hitzeroth |
| MRC Grant 2005-2008 | J Goergens (U Stell), A van Dijk (UNW), I Hitzeroth |
| DST Grant for SA-Cuba collaboration 2007-2010 | A-L Williamson, E Shephard, EU Compuvac team |
| Compuvac EU FP6 Grant | A-L Williamson, E Shephard, C Williamson |
| ♦ DACST / DST = Dept Arts, Culture Science & Technology / Sci & Tech, SA; NRF = National Research Foundation, SA; PRF = Poliomyelitis Research Foundation, SA; MRC = Medical Research Council (SA); CANSA, Cancer Soc SA; CSIR = Council for Scientific and Industrial Research; Stell = Univ Stellenbosch; UP = Univ Pretoria; UFS = Univ Free State; ARC-OVI = Onderstepoort Veterinary Institute; UNW = Univ of the North-West (SA). | |
