Candidate: The candidate has completed his clinical training in both internal medicine and cardiology, and has spent the first two years of a postdoctoral research fellowship studying the molecular genetics of cardiovascular disease. In the last year, the candidate has initiated an investigation into the role of apoptosis in cardiac development and disease, studies that have led to this proposal. As a complement to his basic science interests, the candidate has participated in the clinical research activities of the Heart Failure service, a responsibility that will continue as he joins the Cardiology faculty in July. The RCA will provide invaluable support for the candidate as he makes the transition from postdoctoral fellow to independent investigator, allowing him to acquire new skills in molecular genetics. Environment: Southwestern offers unique advantages for the study of muscle developmental biology. In addition to my mentor, Dr. John Abrams, and principal collaborator, Dr. Eric Olson, several other fly labs and one C. elegans lab are active on campus. This group meets on a weekly basis. Dr. Williams (advisor) lab is actively involved in the study of transcriptional control of striated muscle, and they recently cloned a novel transcription factor that plays a role in muscle development, myocyte nuclear factor (MNF). In addition, the core facilities of both the Departments of Cell Biology and the Division of Cardiology will be available to the candidate. Finally, Drs. Williams (Div. Chief) and Foster (Dept. Chief) are committed to protecting the research effort of the candidate, and have promised to provide independent lab space when appropriate. Research: The long-term goal of the candidate is to understand the fundamental mechanisms that control cell death in the heart. Given that (1) myogenesis and apoptosis are highly conserved processes, and (2) in Drosophila, all cell death converges on one defined genetic locus, while one gene appears to control myogenesis in all muscle lineages, we propose to study the relationship between apoptosis and differentiation in the developing muscle of a model genetic organism, Drosophila melanogaster. This proposal will take advantage of the unique resources listed above.