New Chemical Probes for RNA Structure and Dynamics

通过这一奖项，生命过程化学项目支持马里兰大学学院公园分校的T·夸库·达耶教授和赫尔曼·O·辛蒂姆教授的研究。戴耶教授和辛蒂姆教授将研究核糖开关RNA调控的结构和动态基础，即开启和关闭细菌中的基因调控电路。虽然X射线结晶学已经成为解开与其配体结合的核糖开关RNA性质的有力工具，但它通常无法表征未结合状态。这项提议旨在开发核磁共振(核磁共振)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适当折叠和功能状态的转变的性质。这些努力的一个关键组成部分将是开发技术，以更有效地产生用于核磁共振研究的同位素丰富的RNA。该项目的更广泛影响包括加深我们对基因调控核心的RNA信号的理解。也许最重要的是对参与该项目的学生的教育和培训，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，包括使用核磁共振和计算建模、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重要的细胞催化和基因调控过程。

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.