CORE--Monoclonal Antibody

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This Program Project, of which this Monoclonal Antibody (Mab) Core C is a part, relies heavily in experimental approaches that will provide a multitude of molecules from three potential agents of bioterrorism that are critical for bacterial and viral virulence as well as molecules associated with bacterial ribosome rescue, protein tagging and directed degradation system. It is fully anticipated that Mabs will be made to many if not most of these molecules, and that some will have several functions that could range from identification to possible therapeutic value. Thus, this Core complies with its stated Specific Aim, which is to serve the five Research Projects of this program project, but also to produce reagents useful to Biodefense. The five projects will use a bacterial genomics approach to discovery of molecules : 1) that are required for intracellular proliferation of Yersinia pestis in macrophages (products of rip genes). Mabs to the proteins encoded by rip genes will be important to reveal the underlying basis for Y. pestis proliferation in macrophages (Research Project 1, Bliska). 2) from Francisella tularensis that are involved in the selective inducement of proinflammatory mediators, and that may be involved in the exceptionally high infectivity and virulence of this bacterium (Research Project 2, Furie). 3) from Yersinia pestis and Francisella tularensis, that are involved in the biochemical mechanism of SmpB.SsrA mediated protein tagging and ribosome rescue process. Mabs to these proteins will permit studies on their role in survival, virulence, and pathogenesis of these Category A pathogens (Research Project 3, Karzai). 4) that are required for induction of interferon by hantaviruses that cause deadly Hantavirus Pulmonary Syndrome. Mabs to specific domains of the gtycoproteins and nucleocapsid antigens could have neutralizing activity (Research Project 4, Mackow). 5) of the chaperone/usher pathways of F. tularensis and Y. pestis. Mabs to these proteins will help in determining the roles of these pathways in the pathogenesis of these two Category A bacteria (Research Project 5, Thanassi).