With this award, the Chemistry of Life Processes program is supporting the research of Professors T. Kwaku Dayie and Herman O. Sintim of the University of Maryland at College Park. Professors Dayie and Sintim will examine the structural and dynamic basis of riboswitch RNA regulation, i.e. turning on and off gene regulatory circuits in bacteria. While X-ray crystallography has become a powerful tool to unravel the nature of the riboswitch RNA bound to its ligand, it usually fails to characterize the unbound state. This proposal aims to develop tools such as nuclear magnetic resonance (NMR) spectroscopy and small angle x-ray scattering (SAXS) to provide complementary approaches to better understand the nature of riboswitch transitions from the unbound state to a competently folded and functional state. A critical component of these efforts will be to develop techniques to more efficiently generate isotopically enriched RNAs for NMR studies.
The Broader Impacts of this project include deepening our understanding of RNA signaling at the heart of gene regulation. Perhaps most important is the education and training of students who work on this project, Undergraduate and graduate student researchers on the team will be exposed to a multi-disciplinary training environment, including the use of NMR and computational modeling, synthetic organic chemistry and enzymology, with the goal of understanding how RNA biomolecules control important cellular processes of catalysis and gene regulation at the molecular level.