Cell Biology/Protein Biochemistry of Intracellular ProcessesA strong and diverse group of researchers at Yale study various aspects of cell biology. Paul Forscher (MCDB) is also interested in the molecular events at the leading edge of motile cells. He studies the Aplysia bag cell growth cone, a model system for investigating the cell surface receptors that regulate cytoskeletal and molecular motor protein dynamics. His recent work has centered on the signaling mediated by surface CAMS on the dynamics of actin and myos movements in the growth cone. Mark Hochstrasser (MB&B) studies at a mechanistic and molecular level how specific proteins are rapidly degraded within eukaryotic cells. Such turnover is central to a great variety of regulatory mechanisms, including many of medical relevance. Much of this regulated degradation occurs via the highly conserved ubiquitin-proteasome system. Art Horwich (Genetics) studies the class of chaperones known as “chaperonins” that are large double-ring structures that bind many non-native polypeptides through exposed hydrophobic surfaces in a central channel then productively release them in the presence of ATP. A range of approaches is employed to understand the mechanism of action of these and related components, including: genetic analysis in vivo, structure-function and biochemical analyses in vitro, crystallographic analyses, and fluorescence and NMR spectroscopy studies. Mark Mooseker (MCDB) studies the molecular and functional basis of actin-based molecular motors. The major thrust of current effort is focused on the molecular and functional characterization of actin-€lament based molecular motors — i.e. myosins. Studies include biophysical analyses of single motor molecules using state-of-the art light microscopic imaging techniques, dynamic imaging of myosins in living cells using fluorescently tagged motors, biochemical and structural characterization of purified myosins. Tom Pollard (MCDB) uses a combination of biochemical, biophysical, cellular and genetic experiments to test hypotheses about molecular mechanisms of actin-based cellular movements. His lab studies how assembly of actin filaments pushes forward the leading edge of motile cells. Joseph Schlessinger (Pharmacology) studies the role tyrosine phosphorylation in the control of many cellular processes including cell proliferation, differentiation, metabolism, as well as cell survival and migration. William Sessa (Pharmacology) focuses on how endothelial nitric oxide synthase (eNOS) is regulated in the context of normal physiology and in disease. His lab studies three areas of NO biology:
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