Malaria is endemic to large parts of Africa, and is common in the Northern and Eastern parts of South Africa. It is estimated that worldwide, malaria causes up to 500 million clinical cases and an about three million deaths each year, mostly amongst children under five years of age. The direct and indirect costs of malaria in sub-Saharan Africa, according to the 1997 estimates of the World Health Organisation, exceed $US 2 000 million per annum.
Almost all deaths and severe disease incidents of malaria are caused by Plasmodium falciparum.
This species is becoming increasingly resistant to the current anti-malarial drugs and it is unlikely that a vaccine will be available in the near future. In order to counteract a disease of this magnitude, a multi-faceted strategy is required. The application of structural and functional genomics will open up new prospects for the development of novel, more effective drugs.
A major aim of the malaria research programme is to establish a core expertise in anti-malaria drug development and discovery, which includes:
- Bioinformatic and computational analyses of parasitic traits and properties.
- Recombinant expression of native or E coli codon-adapted synthetic genes of malaria proteins.
- Purification and biochemical characterisation of expressed proteins.
- Comparative structural modelling of selected targets (folate and polyamine pathways).
- Drug discovery either by:
- In silico screening of chemical libraries of small molecules (knowledge-based drug design);
- In silico redesign of existing, but less organism-specific drugs used as templates or
- Screening of isolated plant compounds on malaria cultures (novel chemical scaffolds).
- Rationalisation of the mode of action of drug-leads by gene expression profiling experiments.
- Identification and characterisation of new drug targets.