Measurement of the Deuterium Kinetic Isotope Effect on Hydroxyl Radical Cleavage of RNA

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。最近完成的人类基因组序列，以及许多其他的，提供了原始数据，以建立对生物体如何工作的深刻理解。但是，要了解遗传信息是如何被检索和表达的，需要的不仅仅是基因组中的DNA核苷酸序列。在遗传信息的传递中，一个关键的角色是核糖核酸，RNA。RNA分子的形状对其在细胞生命中的功能至关重要，但很少有方法能够绘制RNA的结构。本项目将开发一种新的实验方法，用于确定RNA结构，该方法利用羟基自由基，一种高分辨率的核酸分子结构化学探针。这种新方法旨在提供RNA结构特征的原子特异性信息。其结果将是一个前所未有的分辨率的RNA结构的化学探针。更广泛的影响。由于RNA分子在所有生物体中无处不在，因此这项研究产生的新结构方法将在世界各地的实验室中广泛应用，以了解RNA在生物学中的作用。研究生谁将在这个项目的工作将接受培训，以采取一个高度定量的方法，通常是定性解释的实验。他们将学习联合收割机合成和物理化学与结构和分子生物学相结合。这个研究项目最初是由两名博士后教师研究员（PFF）开发的，他们每个人都被任命为本科院校的化学助理教授。PFF计划是波士顿大学化学系的一项创新计划，专注于准备最近的博士学位，以教授化学和指导本科院校的研究。PFF的一半时间用于研究，一半用于教学。将寻求新的警察部队成员加入这一项目。Tullius实验室近年来一直致力于向高中生和本科生提供服务，为他们提供在活跃的大学实验室中的研究经验。2009年夏天，四名高中生和一名本科生将在图利乌斯实验室与博士后研究员和研究生一起进行研究。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The recent completion of the sequences of the human genome, and many others, has provided the raw data on which to build a deep understanding of how living organisms work. But more than just the sequence of DNA nucleotides in the genome is needed to understand how genetic information is retrieved and expressed. A key player in the transmission of genetic information is ribonucleic acid, RNA. The shape of an RNA molecule is critical to its function in the life of the cell, yet few methods are capable of mapping the structure of RNA. This project will develop a new experimental method for determining RNA structure that makes use of the hydroxyl radical, a high-resolution chemical probe of the structure of nucleic acid molecules. The new method is designed to provide atom-specific information on the structural features of RNA. The result will be a chemical probe of RNA structure of unprecedented resolution.Broader impacts. Since RNA molecules are ubiquitous in all living organisms, the new structural method that will result from this research will find wide application in laboratories around the world that seek to understand the role of RNA in biology. The graduate students who will work on this project will be trained to take a highly quantitative approach to experiments that normally are interpreted qualitatively. They will learn to combine synthetic and physical chemistry with structural and molecular biology. This research project was originally developed by two Postdoctoral Faculty Fellows (PFFs), each of whom has since been appointed as Assistant Professor of Chemistry at an undergraduate institution. The PFF program is an innovative program in the Chemistry Department at Boston University that is focused on preparing recent Ph.D.s to teach chemistry and to mentor research at undergraduate colleges. Half the time of a PFF is spent on research and half on teaching. New PFFs will be sought to join this project. The Tullius laboratory has focused in recent years on outreach to high school students and undergraduates to provide them with research experience in an active university laboratory. In summer 2009, four high school students and an undergraduate will do research in the Tullius lab alongside postdoctoral fellows and graduate students.