PROJECTS 1, 2, 3 and 4 deal with mechanisms of connective tissue morphogenesis; (1) The processes of procollagen packaging, secretion and assembly into extracellular fibrils; (2) The role and regulation of the degradative side of morphogenesis through control of collagenolysis and proteoglycan degradation in development and tumor invasion; (3) The localization of various collagen and some non collagen macromolecules in the embryonic development of the skeletal cardiovascular and ocular tissues through the use of a variety of monoclonal antibodies, immunohistologic and immunoelectron microscopy; (4) Studies on the supramolecular organization of basement membranes by a number of biophysical and biochemcal approaches. PROJECTS 5, 6, 7, and 8 outline studies designed to further explore the complex cellular and humoral interactions which are responsible for degradation of connective tissues in inflammatory diseases. Projects 5 and 6 explore the role of soluable cellular mediators and cellular interactions on release of products which have the capacity to degrade connective tissue matrices. Project 7 focuses on the structure and composition of collagens and other matrix components of connective tissue and studies factors controlling remodeling of these tissues. Project 8 investigates the biological effects and mechanisms of action of hormones which regulate connective tissues in pathological and non-pathological conditions. PROJECTS 9, 10, and 11 include a study of the biosynthesis of N-glycoproteins by use of chemically synthesized isoprenoid sugar phosphates of known structures, which will serve as acceptors for identification of the products formed, a study of glycopeptides and glycoproteins formed in diseases processes, and a study of the role of sialic acid at the surface of the cell.
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