Malaria caused by Plasmodium falciparum is a major life threatening cause of morbidity in most tropical areas of the world. Drug resistant forms of P. falciparum, mosquito insecticide resistance and possible failure or slow development f malaria vaccines has stimulated the need to identify alternative strategies to combat malaria. New approaches for the control of malaria might emerge from a better understanding of mechanisms regulating gene expression in P. falciparum. Already cloned genes of P. falciparum, the bifunctional dihydrofolate reductase- thymidylate synthase enzyme (DHFR-TS) and a major exported parasite antigen designated p126, will be initially studied to determine important structural attributes of mRNA transcripts and to elucidate key mechanisms regulating gene expression. Study of the regulation of expression of other exported parasite antigens of potential immunological importance will also be undertaken. Transcriptional regulatory elements that control the synthesis and stability of mRNA and mark genes for stage- specific expression will be identified. To facilitate studies of gene expression an in vitro genetic transformation system will be developed. Transient expression of chimaeric genes and stable expression of drug-selectable parasite genetic markers will be studied. In addition, the DHFR-TS gene will be utilized to develop a general method that will identify parasite gene function(s) that are essential for survival of the parasite and are therefore possible anti-malarial targets. These studies will add new insights into the molecular biology of P. falciparum.
