Molecular Biophysics



	William A. Bernhard, Ph.D. We live in an invisible sea of ionizing radiation, consisting of x-rays, g-rays and cosmic rays. Our radiation exposure is increased by its use in medicine and industry. The benefits of these applications must be weighed against the risk of radiation inducing cancer or leukemia. Central to this risk assessment is understanding the mechanisms by which radiation damages DNA. Our group studies these mechanisms using a variety of biophysical techniques, including electron paramagnetic resonance, electron nuclear double resonance, mass spectrometry, and chromatography.

	Barry M. Goldstein, M.D., Ph.D. The structure of a drug, ligand, target enzyme or receptor at atomic resolution ultimately leads to an understanding of its functional properties. Our laboratory uses macromolecular crystallography aimed at determining protein-ligand interactions of molecules with either medical or biotechnology applications. Our studies build on understanding basic enzyme mechanisms and have applications in the rational design of anti-tumor and antiviral drugs and in the design of enzymes to synthesize chemicals in an environmentally friendly way.

	Alan Grossfield, Ph.D. The biophysics of membranes and membrane proteins is critical to understanding the molecular-level mechanisms of a host of biological processes, including signaling, homeostasis, and some forms of immune response. My laboratory is focused on investigating these phenomena using computational techniques, primarily molecular simulation. Presently, we are using molecular dynamics simulations to characterize the membrane-lysing mechanism of antimicrobial lipopeptides, a new class of antibacterial drugs which selectively target bacteria based on differences in lipid headgroup composition. We are also interested in examining GPCR structure and function, peptide-protein interactions, and in developing new methods to represent the membrane environment implicitly and interpret two-dimensional wide angle X-ray scattering experiments on lipid bilayers.

	Thomas E. Gunter, Ph.D. Calcium is a second messenger that activates many enzymes in the cell. We are interested in the physiological properties of calcuim ion transport in the mitochondria and the role of calcium in the regulation of ATP production. Manganese is a toxin believed to use similar ion channels as calcium. Because Manganese is an additive in gasoline fuel, we are investigating the organelles, ion transport properties, target proteins and toxicity of manganese.

	Clara Kielkopf, Ph.D. Noncoding sequences interrupt almost all human genes, and must be removed from pre-mRNAs by splicing before translation into proteins. Our laboratory seeks to understand the structural, thermodynamic, and kinetic characteristics driving protein-RNA and protein-protein interactions during identification and pairing of the the appropriate pre-mRNA splice sites. Given that errors in pre-mRNA splice site identification account for more than 50% of human genetic diseases, and are frequently associated with cancers and leukemias, biophysical maps of the key molecular interactions provide foundations for new therapeutic approaches.

	Joseph Wedekind, Ph.D. The C6666 to U modification of apoB mRNA represents the archetypal RNA editing reaction. This phenomenon requires a Zn-dependent cytidine deaminase, APOBEC-1, which resides at the heart of a multi-protein particle dubbed the nuclear 27S editosome. Other essential proteins include an RNA binding factor (ACF), and a 240 kDa assembly factor. We have undertaken X-ray crystallographic structure determinations of whole 27S particles, as well as isolated proteins in order to elucidate the editosome mechanism. Ultimately this work will establish a working model for mammalian RNA editing.