Our research goal is to understand the molecular events that result in female reproductive development and egg formation. Our studies will take advantage of the biological fact that male worms are necessary to stimulate females to complete reproductive development and to maintain reproductive activity. The significance of the research is that egg production, the end product of reproductive activity, is responsible for the pathogenesis of schistosomiasis. The obtained information should identify potential modes for drug therapy and vaccine development. To accomplish the goal we will: l) Identify and characterize genes that are expressed during the development and function of the female reproductive system. As the male worm controls female reproduction by stimulating vitelline gland development, one focus will be on vitellaria-specific genes. A second focus will be Mehlis gland-specific genes as the Mehlis gland seems to have an important but unknown role in egg production. 2) Once identified, the biological function of the gene products during reproductive development and activity will be elucidated. Determination of when (temporal) and where (tissue, cell) the female-specific gene(s) and gene product(s) are expressed will be made. To study the chemistry of eggshell formation, recombinant gene products representing two putative eggshell proteins will be mixed in vitro with phenol oxidase. 3) To understand how the genes that control female development and egg production are regulated, the 5f flanking regions of the genes which usually contain DNA elements responsible for sex-, tissue- and temporal- specific expression will be studied. Attempts will be made to develop a schistosome transfection system. A well characterized eggshell gene will serve as a model. 4) Once the DNA elements that control gene expression are identified, attempts to identify the regulatory factors and the genes that encode them will be made. Eventually, we hope to understand the mechanism by which the male schistosome regulates female development.
