The University of Colorado School of Medicine will purchase an analytical ultracentrifugation instrument with support from the NCRR Shared Instrumentation Grant Program. This instrument is required to meet the growing demand for the accurate and rapid determination of size, shape, association and interactions of macromolecules and complexes. The increased demand results from expansion of the faculty in several departments in the School as well as the establishment of the interdepartmental Program in Biomolecular Structure. The requested instrument will greatly improve the existing resources and will accelerate research in a broad range of systems, including: ? ? ? Analysis of self-association and heteroprotein interactions in the human progesterone receptor (D.L. Bain) ? ? Obtaining a mechanistic understanding of viral DNA packaging (C.E. Catalano). ? ? De novo design of coiled-coils to understand protein folding and stability and investigations of coiled- coils in native proteins, e.g., motor proteins, transporter of ProP and SARS-coronavirus (R.S. Hodges). ? Determining functional differences of isoforms of progesterone (K. Horwitz). ? ? Examining folding of biologically important RNA molecules including functional RNAs from poliovirus and related viruses, and studying protein-RNA interactions from foot and mouth disease virus (J.S. Kieft). ? ? Analysis of protein assembly mechanisms and quantification of strength of protein-protein interactions in cellular replicases (C. McHenry). ? ? Other areas of current research also include determination of oligomerization and/or protein-protein interactions in a range of receptors (e.g., B cell complement receptor, glycoproteins of coronavirus, ligand binding proteins of estrogen receptor); the role of ETS transcription factors in epithelial cell development and tumorigenesis; subcellular organization of signal transduction pathways; lymphocyte-specific transcription by early B cell factor; storage and intracellular trafficking of lipids; characterization of tissue plasminogen activator protein; characterization of genetically identified telomerase and end-protection complexes in yeast; and molecular mechanisms of pre-mRNA splicing. ? ?
