New Chemical Probes for RNA Structure and Dynamics

有了这个奖项，生命过程的化学计划是支持教授T。Kwaku Dayie和赫尔曼O.马里兰州大学帕克分校的辛蒂姆。Dayie和Sintim教授将研究核糖开关RNA调控的结构和动力学基础，即打开和关闭细菌中的基因调控回路。虽然X射线晶体学已经成为一个强大的工具来解开核糖开关RNA结合到其配体的性质，它通常无法表征未结合状态。该提案旨在开发核磁共振（NMR）光谱和小角X射线散射（SAXS）等工具，以提供补充方法，更好地了解核糖开关从未结合状态到完全折叠和功能状态转变的性质。这些努力的一个关键组成部分将是开发技术，以更有效地产生同位素富集的RNA的NMR研究。该项目的更广泛的影响包括加深我们对RNA信号在基因调控的核心的理解。也许最重要的是对参与该项目的学生进行教育和培训，团队中的本科生和研究生研究人员将接触到多学科的培训环境，包括使用NMR和计算建模，合成有机化学和酶学，目的是了解RNA生物分子如何在分子水平上控制催化和基因调控的重要细胞过程。

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.