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Biological Sciences

Department of Biochemistry

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Biophysics

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Office: 734 Riffe Building
phone: (614) 292-1377
email: Foster.281@osu.edu

B.S. University of Illinois, 1987
Ph.D. University of Utah, 1993
Postdoctoral Fellow, The Scripps Research Institute, 1993-1997

Research Interests: Protein and nucleic acid structure and dynamics, molecular recognition, signal transduction, enzyme catalysis, computational methods, NMR methodology.

Understanding how the structure and mobility of biological molecules influence their function is one of the most exciting and rewarding research objectives in biochemistry, and is the main focus of my laboratory's efforts. Biological processes are coordinated via complex molecular interactions involving proteins, nucleic acids (DNA, RNA) and small molecules. These molecules are not rigid, but rather undergo dynamic conformational changes to achieve their functions. High-resolution NMR spectroscopy is ideally suited to our principle objective of understanding these motions, as it is the only method that allows us to study both the structural and dynamic properties of macromolecules at atomic resolution. Our group enjoys access to outstanding NMR facilities, including spectrometers operating at 600 and 800 MHz, housed in a state-of-the-art Structural Biology Center. While NMR spectroscopy is one major research tool in the laboratory, our projects are fundamentally multidisciplinary and collaborative, merging components of molecular biology, protein engineering and biochemistry, NMR spectroscopy, mass spectrometry and computation. As a result, members of the laboratory have the opportunity and are encouraged to become competent in diverse creative approaches for solving biochemical problems. Group members obtain rigorous training in basic research by studying the fundamental principles that govern biomolecular function, and emerge with scientific skills to pursue careers in either academics or private industry.

Structure and function of nucleic acid binding proteins. Interactions between proteins and nucleic acids are central to fundamental biological processes such as transcription, translation and catalysis. Our laboratory is studying the solution structure of nucleic acid binding proteins in several categories: (1) DNA-binding transcription factors. The objective of these studies is to understand how specificity in protein-protein and protein-DNA interactions allow for the coordinated transcription of specific genes. (2) RNA-binding regulatory proteins. A number of interesting proteins interact with specific elements in the 5' leader regions of the mRNAs of nascently transcribed genes. These interactions are used by cells to regulate the translation of the encoded proteins and transcription of the genes. (3) DNA recombinases. These enzymes catalyze recombination of DNA duplexes by catalyzing strand cleavage and coordinating the rearrangement of the cleaved DNA strands via a Holliday junction. (4) RNase P. This is a ribonucleoprotein complex responsible for the maturation of tRNAs by cleaving nascently transcribed pre-tRNA genes. In eukaryotes, this enzyme consists of one catalytic RNA subunit and several protein subunits. We are working to determine the structures of several of the protein components in order to understand their role in catalysis.

Enzyme structure and dynamics. Enzymes catalyze chemical reactions by binding the appropriate substrates in a conformation that lowers the energetic activation barrier, and then releases the products, at the appropriate rate. While the structures of many different enzymes are known, we have a limited understanding of the molecular motions that enable enzymes to carry out their function. This lack of understanding severely limits our ability to design drugs to specifically inhibit the enzymes, or to design new enzymes to carry out novel chemistries. We seek to understand of the mode of action of select enzymes by characterizing their solution behavior (structure and dynamics) and to examine the effects of inhibitor and substrate binding. We have been studying the dynamic behavior of two classes of enzymes: (1) a metallo-hydrolase and (2) a DNA recombinase.