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Chemical and Bio-enzymatic nucleotide labeling for RNA Structure and Dynamics

用于 RNA 结构和动力学的化学和生物酶核苷酸标记

基本信息

批准号：
1808705
负责人：
Kwaku Dayie
金额：
$ 50万
依托单位：
University of Maryland, College Park
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1808705&HistoricalAwards=false
关键词：
Chemical Bio enzymatic nucleotide labeling

项目摘要

With this award, the Chemistry of Life Processes program is funding the research of Professor T. Kwaku Dayie of the University of Maryland at College Park to examine the structural and dynamic basis of RNA regulation. RNAs are involved in many critical processes in the cell that range from sensing chemicals, speeding up chemical reactions, to controlling virus infections. Yet even though in humans more than 98% of the DNA is used up for making RNA and less than 2% for making proteins, more than 95% of the structures contained in the Protein Data Bank, a repository of 3D structures of biological molecules, belong to proteins and less than 2% of the structures belong to RNAs. This huge disparity stems from the properties of RNAs that make it harder to determine the structures of the RNAs. Professor Dayie develops new methods for the determination of the RNA structure and fill in this critical knowledge gap. These new strategies make RNA more amenable for structural and dynamic studies and facilitate biotechnology applications. The new reagents generated by the research are made available to the community of scientists who study the structure of RNA, including those from industry and from outside USA. Professor Dayie contributes to an outreach program that introduces high school, undergraduate, and graduate students to methods for the study of the structure of RNA and helps them understand how RNA controls signaling in cells. The proposed studies provide critical and new solid phase labeling technologies that can enable the filling of a major gap in RNA structural biology, namely the paucity of RNA structures in PDB. These structures can be used to decipher the molecular basis for the dynamic regulation of gene expression by RNA, which is still poorly understood. Dr. Dayie combines high resolution NMR spectroscopy and small angle x-ray scattering (SAXS) with chemical labeling technologies to study the dynamic basis of RNA signaling. Information from this study provides new insights into biological ligand-induced RNA binding/cell signaling.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通过这一奖项，生命过程化学项目资助了马里兰大学学院公园分校的T·夸库·达耶教授的研究，以考察RNA调控的结构和动态基础。RNA参与了细胞中的许多关键过程，从感知化学物质、加快化学反应到控制病毒感染。然而，即使在人类中，超过98%的DNA被用于制造RNA，不到2%用于制造蛋白质，蛋白质数据库中包含的95%以上的结构属于蛋白质，只有不到2%的结构属于RNA。蛋白质数据库是一个生物分子的三维结构的储存库。这种巨大的差异源于RNA的性质，这使得确定RNA的结构变得更加困难。大业教授开发了确定RNA结构的新方法，并填补了这一关键的知识空白。这些新战略使RNA更适合于结构和动态研究，并促进生物技术应用。研究产生的新试剂可供研究RNA结构的科学家社区使用，包括来自工业界和美国以外的科学家。大业教授参与了一个推广项目，向高中生、本科生和研究生介绍研究RNA结构的方法，并帮助他们了解RNA如何控制细胞中的信号。提出的研究提供了关键的和新的固相标记技术，能够填补RNA结构生物学中的一个主要空白，即PDB中RNA结构的缺乏。这些结构可以用来破译RNA动态调节基因表达的分子基础，这一点仍然知之甚少。大业博士将高分辨率核磁共振波谱和小角X射线散射(SAXS)与化学标记技术相结合，研究RNA信号的动态基础。这项研究的信息为生物配体诱导的RNA结合/细胞信号提供了新的见解。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。