The ability to elucidate the primary structure of extremely small (picomole) amounts of biologically relevant proteins has had a profound impact in the biological and medical sciences. This capability, due to the recent development of protein microsequencing and amino acid analyzing technologies, has extended our knowledge of the structure and function of normal and abnormal proteins in health and disease. Furthermore, with the recent advances in the fields of recombinant DNA and genetic engineering, protein microsequencing is often a mandatory first step necessary for the design and synthesis of specific DNA probes needed to study gene structure and function. This proposal is to place a state-of-the-art research-grade protein microsequencing laboratory (PMSL) into a hospital environment for use in a variety of research projects. Potential uses for such a device in our hospital include the study of: 1) the non-enzymatic glucosylation of proteins in diabetes mellitus; 2) the molecular pathology of Alzheimer's disease and other degenerative diseases of the nervous system; 3) the primary structure and regulation of human atrial natriuretic factor; 4) the structure and function of von Willebrand's factor; 5) the characterization of cytokine products of T-cells; 6) the gene products of thyroid hormone action; 7) the primary structure of endogenous digoxin-like compounds; 8) insulin receptor phosphorylation and structure; 9) the structure and function of thyroid hormone-regulating enzymes; 10) the regulation of platelet-endothelium interactions in thrombosis and atherosclerosis; 11) the structure of active sites of adenylate cyclase; and 12) the structure and function of mutant viral DNA polymerase. The PMSL will become a central feature of the research efforts of many investigators at the hospital and will greatly enhance our ability to make progress in these several areas.