TGFB-LIKE SIGNALING IN THE PARASITE SCHISTOSOMA MANSONI

Cornell University Ithaca, Ithaca NY

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Abstract

Schistosomiasis, which results from infection by a parasitic trematode, affects approximately 200 million people worldwide. Despite the availability of appropriate diagnostics and effective treatments, re- infection and sequelae of chronic infection remain major health concerns. The migration of Schistosoma mansoni in the human host likely depends upon host-derived factors which provide signals for the parasite. Understanding the intricate interactions between host and parasite may suggest methods to prevent the development of a patent infection. The S.mansoni receptor kinase (SmRK1), a transforming growth factor-beta (TGFbeta) receptor-like molecule on the surface of the parasite, is a likely candidate for mediating parasite development and host-parasite interactions, since members of the TGFbeta superfamily are known to he involved in a variety of developmental and growth regulatory processes in a wide range of species. The goal of this proposal is to examine the function of SmRK1 by demonstrating that the receptor can transmit signals in a mammalian TGFbeta-like system, by cloning the components of the receptor signaling cascade from a parasite cDNA library, by demonstrating that ligands from either the host and/or the parasite can stimulate receptor activity, and by disrupting expression of the receptor in the maturing parasite to reveal its role in development within the host.