The Science Core exists to provide reagents and services to the various projects within this Program project grant, and to the Neuropathology and Animal cores. The need for specific reagents and services are often common to multiple projects and cores, as they are for the projects on other Program project grants. The most efficient method of operation for providing reagents and services requiring complex, expensive equipment is therefore via a central core with a highly skilled staff. For this renewal ofthe Program project, the Science core will provide recombinant mouse PrP (with and without isotopic labels) for the generation of synthetic mammalian prions, and anti-PrP antibodies, for Project 1. Recombinant Sup35 will be produced for Project 2, in addition to constructs of Sup35 for development of transgenic mouse lines. The Science core will provide fluorescence activated cell sorting, and prepration of various A-beta aggregates (both synthetic and extracted from natural sources), for Project 3. Anti-PrP antibodies including recombinant Fabs will be supplied to the Neuropathogy core (Core C). The Animal core (Core D) will be supplied with isotopically labeled mouse diet in support of Project 1, and screening of all transgenic lines in suport of Projects 1, 2 and 3. Leadership for the Core will be provided by Dr. Kurt Giles, and Assistant Professor with over 15 years experience in neurodegenerative disease research, and by Dr Michael Silber, a Professor with over 30 years industrial and academic experience, who will act as co-director. Drs. Giles and Silber will be assisted by other scientists and research associates to provide the above functions. RELEVANCE (See instructions): Understanding the molecular pathogenesis of prion diseases is central to ultimately developing treatments for a range of nerudegenerative disorders. The Science core supports the other projects and cores by supplying a range of reagents and services in a centralized and efficient manner.