Lab Research Focus: Biochemical Properties of the Collagens
Over the past years, our investigations on connective tissues have been instrumental in establishing that collagen molecules collectively represent a family of chemically distinct, though functionally related, proteins. The physiological significance of the different types of collagen is underscored by additional observations indicating that molecules belonging to individual molecular species within the collagen family generally form unique and readily distinguishable functional aggregates within the extracellular spaces of various connective tissues. Our current research efforts are devoted largely to addressing several key issues relevant to the molecular diversity of the collagen family.
Analytical Systems. A portion of our efforts is focused on the development of analytical systems to determine the proportion of different collagens in connective tissues. The systems rely on chemical fragmentation of the molecules in situ and chromatographic resolution of marker peptides specific for various collagens. Application of these techniques to major components of the skeletal and cardiovascular systems is providing a detailed view of chain utilization in the construction of various molecular species of collagen.
Physiological Significance of the Unique Fibrillar Collagens. The precise rationale for the existence of five unique fibrillar collagen systems in mammalian organisms is currently unknown. We have shown in recent studies that certain molecular species of the fibrillar collagens are highly active in binding and immobilizing portions of protease inhibitors. The bound inhibitor fragments retain the inhibitory capacities of their parent molecules and therefore may serve to protect collagen fiber systems and other elements of the extracellular matrix from degradation. The system of greatest potential interest in this regard is type III collagen. Initial results suggest that this collagen may serve as a unique connective tissue reservoir for an active-center fragment of a-1-antitrypsin. The physiological role for type III collagen may thus be more related to chemical defense mechanisms than physical structure and stability.
Collagen as a Carrier for Chemical and Biological Agents. In other studies, the role of collagen as a vehicle for implanting bone morphogenetic factors at localized sites for the purpose of enhancing bone repair has been explored. Early results in these studies have been considerably extended and a rabbit cranial repair model has been developed and utilized to demonstrate that experimental implants completely restore the entire top of the cranium after surgical excision. We sought and have obtained approval to extend these studies to human patients for the purpose of facilitating restoration of craniofacial bone defects.
Edward J. Miller (b. 1935) Professor of Biochemistry and Molecular Genetics, completed undergraduate studies at Spring Hill College (B.S. 1960) and did graduate work in Radiation Biology and Biophysics at the University of Rochester (Ph.D. 1964). He pursued postdoctoral studies at NIH before becoming a staff member there in 1966. Dr. Miller came to Birmingham in 1971. He has served on the editorial boards of several journals. His research is supported by grants from NIH.