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. After probes are synthesized and used to identify genes, both sequencing of the DNA as well as synthesis of both peptides and additional DNA sequences from regions of the DNA sequence are necessary. These peptides are then used as immunological probes. This proposal is to place a state-of-the-art research grade protein and DNA sequencing system as well as protein synthesis into this hospital environment for use in a variety of basic research projects relating to biopolymers. Potential users for such biopolymer equipment in non-clinical research include the study of: (1) the molecular pathology of Alzheimer's disease and other degenerated diseases of the nervous system; (2) the isolation of the gene for human ferrochelatase; (3) post-translational modification of proteins; (4) molecular biology of human myeloid differentiation; (5) pulmonary surfactant proteins; (6) ionizing radiation-induced DNA damage and repair; (7) purification of the Type II thyroxine 5' deiodinase and cloning of its gene; (8) site- specific mutagenesis of von Willebrand's factor; (9) biochemistry, molecular biology and biological action of eosinophil and basophil proteins; (10) molecular biology of the polio virus receptor. The Biopolymer Lab will be placed in a laboratory dedicated to synthesis and structure studies and will become a central feature of the research efforts of many investigators at the hospital; it will greatly enhance our ability to make progress in these several areas.
