PROJECT SUMMARY STRUCTURAL BIOLOGY CORE The Emory-Sage-SGC-Jax TREAT-AD Center Structural Biology (Struc Bio) Core, led by MPI Dr. Aled Edwards, aims to provide Target Enabling Packages (TEPs): a combination of experimental tools and knowledge that will allow researchers to investigate the biology of potential AD drug targets and to test therapeutic hypotheses. The TEPs will consist of: gene knockout reagents and cell lines; purified target proteins for functional studies and for the development of antibodies and inhibitors; and structures of proteins and protein:ligand complexes, to understand protein functions and support drug development. Target selection and the definition of the required experimental tools will be determined in consultation with the Bioinformatics and the Admin and Data Cores. The Structural Biology Core will have a central role within the Center, providing purified proteins for assay development and screening by the Medicinal Chemistry and Assay Core and structural data to guide chemical development by the Medicinal Chemistry Core. By releasing all reagents and data, we will enable and promote deeper and wider study by the biomedical research community. The specific aims of the StrucBio Core are: 1. Identify selective and potent antibodies to aid in target characterization. 2. Express and purify recombinant target proteins. 3. To characterize small molecule screening hits. 4. Generate high-resolution structures of the proteins with small molecules bound.