Malaria is a major health problem in many countries of the world, causing about 2 million deaths annually. The increasing spread of drug-resistant malaria parasites and insecticide-resistant vectors has stimulated the research and development of new control strategies. One strategy, focusing on the development of transmission-blocking vaccines, has resulted in the characterization of a few sexual stagespecific antigen genes. The identification of new targets for vaccine and drug development depends on the expansion of our understanding of various molecular and cellular processes of the parasite. Although malaria sexual stages are essential for the continued transmission of the disease, the molecular mechanisms governing sexual development of the parasite are largely unknown. To elucidate the molecular mechanisms underlying sexual development in Plasmodium falciparum, the interaction between an evolutionarily conserved RNA-binding protein (RBP) and its target mRNA(s) will be characterized at the molecular level. In other organisms, the best characterized members of this RBP family bind to 3' untranslated regions of their target mRNAs and repress their translation. The association of RBP members with germline cells in other organisms and the differential expression of the P. falciparum RBP in sexual stages suggest a related function for this protein in sexual differentiation and development of the malaria parasite. The proposed studies will evaluate this hypothesis by cloning the P. falciparuin RBP and characterizing its expression pattern, subcellular location, and specific interaction with the target mRNA(s). The target genes will be isolated and analyzed by employing the yeast three-hybrid system and in vitro binding assays. The biological functions of the RBP and its target gene(s) will be genetically studied using targeted gene disruption techniques. The results of these studies will elucidate the importance of translational control in sexual development and contribute to our understanding of the fundamental molecular biology of the parasite, which may eventually lead to the finding of novel targets for malaria control.
