New Chemical Probes for RNA Structure and Dynamics

用于 RNA 结构和动力学的新型化学探针

• 批准号: 1213668
• 负责人: Kwaku Dayie
• 金额: $ 30万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1213668&HistoricalAwards=false
• 关键词: New; Chemical; Probes; RNA; Structure

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.

通过这个奖项，生命过程化学项目正在支持马里兰大学帕克分校的T. Kwaku Dayie教授和Herman O. Sintim教授的研究。Dayie和Sintim教授将研究核糖开关RNA调控的结构和动态基础，即在细菌中打开和关闭基因调控回路。虽然x射线晶体学已经成为揭示核糖体开关RNA与其配体结合的本质的有力工具，但它通常无法表征非结合状态。该提案旨在开发核磁共振（NMR）波谱和小角度x射线散射（SAXS）等工具，以提供互补的方法，以更好地理解核蛋白开关从非结合状态到有效折叠和功能状态的转变的本质。这些努力的一个关键组成部分将是开发技术，以便更有效地生成同位素富集的rna，用于核磁共振研究。该项目的广泛影响包括加深我们对基因调控核心RNA信号传导的理解。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催化和基因调控的重要细胞过程。