Malaria is a mosquito-borne disease that is difficult to control due, in part, to the development of drug-resistant Plasmodium parasite strains and insecticide-resistant mosquitoes. Therefore, it is necessary to develop innovative strategies to supplement now ineffective malaria control measures. The proposed research, which will investigate a key developmental transition of malaria sporozoites, should provide valuable information concerning the genes that influence or control sporozoite infectivity for the mosquito and vertebrate host. Previous studies have shown that structural as well as infectivity differences exist between sporozoites isolated from mosquito midgut oocysts and those isolated from salivary glands. It is postulated that these developmentally-regulated differences result from differential gene expression. Thus, this project is designed to identify stage-specific genes responsible for the structural differences and then assess if these genes are responsible for the observed differences in infectivity. cDNA libraries, representing the transcription products of sporozoite genes from the two stages, will be screened using a subtractive methodology and stage-specific clones will be isolated. These cDNA clones will be characterized by DNA sequencing, sequence analysis, Southern blotting, immunolocalization, and Northern analysis or in situ hybridization. The expression products of unique cDNA clones then will be assessed for infectivity for mosquito salivary glands or the chicken vertebrate host by in vivo or in vitro competitive-blocking experiments. Determination of the genes responsible for differential infectivity may permit the development of new ways to prevent disease transmission by the mosquito vector.
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