The Core's mission is the scientific and administrative support of all four Projects in the Program, providing a standardized source of reagents, resources, and protocols. A Chemistry Component will design, synthesize, and test enzyme inhibitors for potency and selectivity in vitro and in vivo before passing them on to Projects 2 and 3/4 for co-crystallization studies and pharmacological analysis, respectively. A Biochemistry Component will provide pure proteins to Program Projects 1 and 2 for functional and structural studies, respectively. A Mouse Component will manage the breeding, crossing, and distribution of genetic mouse models. These three scientific arms of the Core will combine to provide the best and most consistent reagents for use in the research aims of the Program Project as a whole. Finally, a small Administrative Component will ensure fiscal responsibility, seamless communication, and proper documentation.