PROJECT SUMMARY Our broad, long-term objectives are to supply reagents, models and expertise from a centralized Science Core facility to all participants of the Program Project. Core operation represents a balance between providing services based on established procedures, and continued innovation in methods and protocols. Safety is a particular guiding principle of the Core, and is addressed by the many years of experience of Core participants in the study of prion diseases, facilities for safe homogenization and other biohazard operating procedures, prion handling and decontamination. Protocol standardization is another crucial goal, so that all aspects of the Program Project have access to reagents and services produced and operated using consistent methods from a constant, reliable source. The Science Core proposes five Specific Aims to accomplish this goal: Aim I will produce and supply characterized mouse models of prion disease and tissues from those mice; Aim II will supply purified anti-PrP monoclonal antibodies (mAbs) with well-defined properties; Aim III will supply preparations of purified infectious prions; Aim IV will quantify prions using sensitive, high throughput cell-based assays; and Aim V will perform detailed biochemical, biophysical and structural studies of prion strains. The Science Core has shown itself to be capable of adapting to efficiently incorporate elements of previous Core structures as well as providing expanded state of the art facilities, techniques and skills for the entire Program Project. The longstanding experience of the Core Co-Directors, Dr. Telling and Dr. Soto, and Associate Director Dr. Bian, is a significant strength. The Science Core resides in outstanding environments for studies of prion diseases. Studies within individual Projects will be conducted in close collaboration with the Science Core to take advantage of the availability of models and expertise, standardized and consistent methodologies, and uniformly consistent, high quality reagents. The activity of the Science Core is essential for the successful accomplishment of Program goals.