The overall goal of the project is to develop specific, effective and safe strategies for the treatment and prevention of opportunistic infection with the parasite Cryptosporidium parvum. This parasite is a significant cause of human gastrointestinal disease worldwide. There is currently no effective specific therapy approved for this disease. The approach taken to identify new therapeutic strategies is based on understanding the biology and pathogenic mechanisms of the parasite. The proposal is focused on establishing the functional role of two C. parvum glycoprotein gp40 and gp15, which are likely to be involved in attachment and invasion and are encoded by a single gene, Cpgp40/15 and on molecular and biochemical characterization of these proteins and their glycotopes. The functional role of these proteins will be established by competitive inhibition studies on attachment and infection. The relative roles of the carbohydrate and protein moieties of gp40 and gp15 will be evaluated and the determinants involved in these processes mapped. The relationship between gp40 and gp15 will be determined, expression in various lifecycle forms determined and the membrane anchoring and glycosylation determined. These studies will enable future assessment of the role of these glycoprotein on infection in vivo using animal models of cryptosporidiosis and identification of host cell receptors for them and ultimately determine if infection can be prevented or treated using these glycoprotein as targets.
