The long term objective of this proposal is to elucidate the function of the Schistosoma mansoni surface membrane serine/threonine kinase. It is anticipated that work directed towards accomplishing the Specific Aims will provide important new insights into the molecular basis of helminth parasitism.
The specific Aims of this proposal are: 1) to fully characterize the schistosome surface membrane type I receptor serine threonine kinase; 2) to identify the ligand for the schistosome type 1 receptor serine threonine kinase. A gene, sm RSTK-1, which is believed to encode the receptor is to be expressed in order to make recombinant receptor. The recombinant receptor will be used to raise anti-receptor antibodies. These will be used to localize the receptor on the worm and, in blocking experiments, to study receptor function. The receptor protein, receptor gene and anti-receptor antibodies will be used as probes to facilitate the identification of parasite proteins which interact with the receptor. The yeast two-hybrid system and co-precipitation experiments will be used for these studies. The ligand specificity of the receptor will examined by expressing the smRSTK-1 gene in mammalian cells and investigating which of known potential ligands, or parasite derived molecules, it will bind. Despite the availability of an excellent drug (praziquantel) and its widespread use, the incidence of schistosomiasis has not decreased. In combination with immunological and pharmacological studies directed towards specifically developing preventatives or cures, it seems prudent to continue to attempt to understand more of the basic biology of this relatively little understood group of important pathogens. Studies of the type proposed herein have the potential to provide a rational approach for developing appropriate therapeutics or prophylaxis (immuno-of-chemo-) for interrupting schistosome infection.
