International Collaboration in Chemistry: Single-molecule FRET

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This International Collaboration in Chemistry award from the Chemistry of Life Processes Program in the Chemistry Division of the National Science Foundation supports Dr. Scott Blanchard, from the Joan and Sanford I. Weill Medical College of Cornell University, to study a mechanism of translation control whereby elements typically residing within the 5'-untranslated region of messenger RNA (mRNA) bind small-molecule metabolites to control gene expression. Such elements are generally referred to as riboswitch domains. The work includes an international collaboration with Dr. Ronald Micura, from the Leopold-Franzens University (Innsbruck, Austria). Dr. Micura's work is supported by the Fonds zur Forderung der wissenshaftlichen Forschung (FWF) in Austria. A critical aspect of gene expression in all cells is the translation of mRNA templates into specific protein molecules that carry out a broad array of essential life processes. Translation of mRNA is carried out by the ribosome, a two subunit RNA-protein assembly composed of more than fifty individual gene products. Control of gene expression at the level of translation, which is essential to cell survival, can be mediated by numerous mechanisms. The goal of the research is to understand which specific steps in the translation process are affected by the riboswitch response to small-molecule binding. To achieve the goal, the research team will engage a battery of physical and organic chemistry initiatives that will directly image riboswitch-mediated regulation of ribosome-catalyzed translation at the single-molecule scale. In so doing, the team will explore fundamental aspects of the riboswitch regulation mechanism with a special emphasis on the dynamic properties of the system and how such features are regulated by ligand/metabolite binding interactions. The international collaborative research proposed is designed to provide an opportunity for undergraduate, graduate and post-graduate students from distinct research programs to receive interdisciplinary training in organic chemistry and single-molecule fluorescence. This experience will enable the development of new biophysical approaches and experimental techniques for single-molecule research that can be generally applied to the imaging of dynamic life processes at the molecular scale.