RECOGNITION OF THE CS PROTEIN BY LIVER CELL RECEPTOR

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The main theme of the Program Project is the characterization of the mechanism of recognition of a sporozoite ligand, the region II-plus of the circumsporozoite (CS) protein, by heparan sulfate proteoglycan (HSPG) receptors, on the plasma membrane of hepatocytes. The ultimate goal of our projects is to provide a rational basis for the development of chemoprophylactic and immunoprophylactic agents which can prevent malaria infection. This Program Project consists of three projects and an administrative as well s three Scientific/technical Cores: Project 1 - Structure and function of region II-plus of the CS protein. Its main objective is to define more precisely the sporozoite ligand, i.e., the region II-plus motif of the CS protein and to correlate its structural features with its binding affinity for the HSPG receptor. Project 2 - Structure and function of the liver receptor of CS protein. This project aims to characterize the core protein of the CS-binding HSPG and the structure and composition of the GAG chains. Project 3 - Immunological study of the CS ligand and its liver cell receptor. Its main objective is to define immunogens that can induce antibodies which block the interaction of sporozoites with their receptor on liver cells. The Administrative core will provide administrative support and scientific coordination ot all projects. The Scientific/Technical cores will provide sporozoites of rodent malaria [Insectary core - b], synthetic peptides and MAPs [Peptide synthesis facility - c], as well as E.M. support [E.M. facility - core d] for all three projects.