FIP Seminar: From fluctuations to function: The role of dynamics in gene expression and biomolecular function

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Wed, 02/22/2017 - 12:00 to 13:00

Ruben Gonzalez


Dr. Ruben Gonzalez - Professor, Department of Chemistry, Columbia University

Over the past two decades, stunning breakthroughs in the field of structural biology have continued to produce groundbreaking high-resolution structures of large, multi-component biomolecular machines. Comparative analyses of these static structures reveals the remarkable conformational flexibility of these machines and hints at the significant structural rearrangements that evidently accompany their functional cycles. Unfortunately, the experimental observation and characterization of these conformational dynamics is severely impeded by the size and complexity of biomolecular machines, severely limiting our understanding of the contributions that dynamics make to their functions. Using a combination of molecular genetic-, biochemical-, and single-molecule biophysical approaches, my research group aims to overcome these challenges and elucidate the precise roles that the conformational dynamics of biomolecular machines play in driving and controlling their functions. My seminar presentation will primarily focus on our studies of the mechanism and regulation of messenger RNA translation into protein by the ribosome, an essential step in gene expression. Specifically, I will discuss how thermally driven fluctuations of the ribosome and other essential translation components contribute to the mechanism and regulation of translation. Because the ribosome is the target of over half of all currently prescribed antibiotics and because of the growing list of human diseases to which deregulation of translation has been causally linked, our findings hold great promise for informing the development of next-generation antibiotics and small-molecule therapeutic agents that function by modulating the conformational dynamics of the translation machinery. Building on what we have learned from these studies, I will close my presentation by describing recent technological advances that are allowing us to investigate biomolecular dynamics which play important roles in gene expression and cellular physiology, but that have thus far remained difficult or impossible to investigate.

Ruben Gonzalez graduated cum laude from Florida International University (FIU) with a B.S. in Chemistry and Biochemistry in 1995. While at FIU, Ruben conducted undergraduate research with Prof. Stephen Winkle in the Department of Chemistry and Biochemistry, where he investigated the thermodynamics and kinetics of protein and carcinogen binding to unusual DNA structures. Notably, Ruben's research in Prof. Winkle's laboratory demonstrated that RNA polymerases could specifically recognize unusual DNA structures formed at the junction of B- and Z-form DNA.

Ruben next moved to the Department of Chemistry at the University of California, Berkeley to conduct his doctoral research with Prof. Ignacio Tinoco. While in Prof. Tinoco's laboratory, Ruben's research interests focused on the structure and thermodynamics of a specific RNA structure, known as an RNA pseudoknot, which is involved in the translational control of gene expression in many viruses. In particular, Ruben was interested in how specific binding of divalent metal ions stabilize RNA pseudoknot structures. As part of his research in Prof. Tinoco's laboratory, Ruben helped develop now widely-used methodology for using cobalt (III) hexammine as a mimic of magnesium (II) hexahydrate in order to determine the solution structure of a divalent metal ion binding site in an RNA pseudoknot using nuclear magnetic resonance spectroscopy.

Upon obtaining his Ph.D. in Chemistry in 2000, Ruben moved to Stanford University where he conducted postdoctoral research as an American Cancer Society Postdoctoral Fellow in the laboratories of Prof. Joseph D. Puglisi in the Department of Structural Biology and the former United States Secretary of Energy Prof. Steven Chu in the Department of Physics and Applied Physics. While at Stanford, Ruben helped integrate expertise from Profs. Puglisi's and Chu's laboratories in order to pioneer the first single-molecule fluorescence investigations of the ribosome, the universally-conserved RNA-based molecular machine responsible for protein synthesis in all living cells.

Ruben joined the Department of Chemistry at Columbia University as an Assistant Professor in 2006 and was promoted to Associate Professor without Tenure in 2011, to Associate Professor with Tenure in 2012, and to Full Professor in 2015. Research in his laboratory focuses on the biophysical chemistry and biochemistry of nature's molecular machines, with significant emphases on fundamental biological processes executed by RNA- and ribonucleoprotein (RNP)-based machines. Ruben serves on the Editorial Board of the Journal of Molecular Biology, as a Regular Member and rising Chairperson of the Molecular Genetics A Study Section at the National Institutes of Health, and has most recently has been elected to the General Council of the Biophysical Society. Research in Ruben's laboratory has been recognized with numerous awards, including a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, a National Science Foundation CAREER Award, an American Cancer Society Research Scholar Award, a Columbia University RISE Award, a Distinguished Columbia Faculty Award, a Camille Dreyfus Teacher-Scholar Award, and, most recently, Ruben has been selected as a Scientist to Watch by The Scientist and as a finalist for a Blavatnik National Award for Young Scientists.