Plasmodium falciparum contains a multi-membraned plastid of apparent algal origins. The 35 kb plastid genome contains highly conserved genes, suggesting that the plastid's presence is beneficial or necessary in the parasite. This proposal will generate tools to investigate the requirement for the plastid in erythrocytic and insect stages. Expression of two plastid genes will be characterized by analyzing stage-specific expression at RNA and protein levels. This characterization will identify the times at which the plastid appears most active in the life cycle. Antibodies generated for this experiment will also be used to develop a system to analyze plastid protein synthesis. Sequences on the plastid genome suggest that organelle function(s) might be selectively inhibited by certain compounds which would not affect host functions. Previous reports of plastid-targeting drugs have described inhibition of culture growth but failed to conclusively show preferential inhibition of plastid genome expression. P. falciparum cultures treated with drugs will be assayed for the selective effects on plastid protein synthesis. Of additional interest will be monitoring the effects of selective plastid inhibition on parasite growth. The experiments outlined in this project will address the questions surrounding the need for plastid conservation and ascertain the potential of the plastid as a target in much-needed antimalarial chemotherapy.
