Research Topics
Department of Biochemistry
Ph.D. (1971) University of California, San Diego
Research Topics
Research Interests
A major theme of research in my laboratory concerns a new model of biological membrane structure involving the existence of lipid and protein domains. We have developed methods using fluorescence digital imaging microscopy to directly visualize and quantitate the lateral heterogeneity, or domains, present in membranes. One series of experiments involves the hypothesis that many components of signal transduction pathways are organized into functional domains. When a growth factor or hormone stimulates a cell, it first binds to a receptor in the plasma membrane and this triggers a cascade of events that depends on the type of cell. If the components are organized into a domain this would greatly increase the specificity and efficiency of the process. This has been most closely studied with the membrane factors that activate protein kinase C and result in the phosphorylation of different proteins. The activators, substrates, and the enzyme can be organized into domains that produce faster rates of reaction. This also provides a novel level of regulation for the signal transduction process.
A second research area involves understanding the mechanisms that coordinate the rates of macromolecular synthesis and regulate cell growth. Adenylate kinase is key to this regulatory process through its control of AMP and ATP levels in the cell. Site specific mutagenesis of the cloned gene is being used to examine the role of critical amino acids for the structure and dynamic properties of the enzyme.
A third research area involves understanding the growth factors and other molecules that influence the development of oligodendrocytes leading to the formation of myelin. Neurons produce a mitogen for oligodendrocyte progenitor cells and influence their differentiation. The molecular mechanism of these processes is being studied in co-cultures of cells of the oligodendrocyte lineage and neurons obtained from dorsal root ganglia.
Potential applications of this research involves evaluating dietary modifications on cell membranes and the development of drugs to treat disorders dealing with lipid metabolism, demyelination, transmission of viral diseases, and uncontrolled growth of tumor cells. Other methodology of potential interest to industry is the application of fluorescence methods to biological problems.
Key Words
Animal Cell and/or Tissue Culture, Image Analysis, Membrane
Structure and Function, Protein Purification and Characterization, Neurobiology,
Structural Biology, Site-Directed Mutagenesis, Lymphokines/Growth Factors, Virology