MECHANISM OF HOST INVASION BY SCHISTOSOMES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Characterization of the molecular mechanisms of host invasion by schistosomes will be an important step in developing rational approaches to prevention or control of schistosomiasis. Our interest is in studying the biochemical and molecular mechanisms by which a proteolytic mixture, elaborated by schistosome larvae in response to lipid, facilitates degradation of host extracellular matrix and entrance of infectious larvae into the host bloodstream. This project combines chemical proteomics techniques with the wealth of recently available schistosome genomic sequence data to examine the key protein components that facilitate host invasion. Our methods include protein separation techniques followed mass spectrometric analysis of the proteins. We then analyze the derived protein sequences using bioinformatics and sequence analysis tools available through the Computer Graphics Laboratory. A related project is in studying schistosome proteolytic enzymes used for digestion of the host hemoglobin and other plasma proteins and for propagation of infection. Specifically, we are interested in mapping out the biochemical activation cascade for the schistosome digestive proteases. A new project has been started: The interaction of Trypanasome brucei rec Cathepsin B with Transferrin and the identification of cleavage sites. For these projects, we use CGL resources for structural modeling and sequence analysis of the schistosome proteolytic enzymes.