DESCRIPTION (from the application): The importance of deciphering basic mechanisms of apoptosis, both for understanding the pathogenesis and designing treatment for the many diseases featuring cell death dysregulation, has become increasingly clear over the past several years. Apoptosis has been implicated in age-associated degenerative conditions such as Alzheimer's disease and amyotrophic lateral sclerosis, developmental neurodegenerative conditions such as spinal muscular atrophy, progressive myoclonus epilepsy and Batten's disease, stroke, neoplasias (which also have a strong age association), autoimmune diseases, myocardial infarction, retinal degeneration, and other diseases. To answer the surge of interest in apoptosis over the past several years, in 1996 we established a postdoctoral training program mentored by an experienced group of interactive apoptosis investigators. The training program takes advantage of the high concentration of experienced and highly active apoptosis researchers at the Burnham Institute (John Reed, Dale Bredesen, Guy Salvesen, Steven Frisch, Erkki Ruoslahti, Kathryn Ely, Nuria Assa-Munt and Stuart Lipton) and the nearby La Jolla Institute for Allergy and Immunology (Douglas Green, Carl Ware and Donald Newmeyer). This program offers individuals who have recently received the Ph.D. or M.D. degree, and who have demonstrated exceptional potential and dedication for a career in research, a wide array of proven approaches to the study of the basic mechanisms and disease relevance of apoptosis. Specifically, advantages of the proposed program include the active faculty (with over 300 publications in the field), the local biomedical community (which includes the Salk Institute, Scripps Clinic and Research Foundation, the University of California, and several area biotech/ pharmaceutical companies with active efforts in apoptosis), a strong history of training fellows in this area, and a large number of complementary approaches and techniques. These include an embryonal stem cell facility, cell-free and simple genetic apoptosis systems (developed by members of the program), structural biology (both X-ray crystallography and nuclear magnetic resonance), phage display, yeast 2-hybrid systems, computational biology, protein purification, physical chemistry techniques, and others. Trainees completing the program are highly qualified to become successful independent scientists. We seek a renewal of this successful fledgling program.