The long term objective of the Physician Scientist Award application is to develop an independent biomedical research career in cellular biology and apply this subspecialty to the study of schistosomiasis. Phase I will consist of 2 major divisions. First, a fundamental background in cell biology will be developed utilizing graduate school courses, seminars, journal clubs and informal discussions. A committee will oversee the progress of the candidate. Second, a research project on the biology of surface maturation of Schistosoma mansoni will be initiated under Drs. Kenneth Miller and G. Richard Olds of Brown University. These studies will investigate surface maturation during the transformation of infective cercariae to larval schistosomula, a critical period when the parasite must adapt from a free-living to a parasitic existence. First, the role of second messengers in initiation of surface maturation will be investigated. Next, since microtubule inhibitors prevent surface maturation and reduce the ability of schistosomula to mature into adult worms, microtubules will be studied in depth. Finally, schistosomula surface antigens will belocalized within cercariae using immunocytochemistry. Detection of antigens within cercariae may suggest that vaccines against schistosomiasis could be prepared from the cercarial stage. At the completion of 2 years the candidate will have developed basic skills and education to pursue independent research during Phase II. This research will be a continuation of the study of schistosomes surface membranes. Understanding the cell biological mechanisms of membrane maturation during the cercarial-schistosomula transformation may allow development of new strategies to interrupt transmission of schistosomiasis.
