International Collaboration in Chemistry: Single-molecule FRET

化学国际合作：单分子 FRET

• 批准号: 1223732
• 负责人: Scott Blanchard
• 金额: $ 30万
• 依托单位: Joan and Sanford I. Weill Medical College of Cornell University
• 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: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1223732&HistoricalAwards=false
• 关键词: International; Collaboration; Chemistry; Single; molecule

This International Collaboration in Chemistry award from the Chemistry of Life Processes Program in the Chemistry Division of the National Science Foundation supports Dr. Scott Blanchard, from the Joan and Sanford I. Weill Medical College of Cornell University, to study a mechanism of translation control whereby elements typically residing within the 5'-untranslated region of messenger RNA (mRNA) bind small-molecule metabolites to control gene expression. Such elements are generally referred to as riboswitch domains. The work includes an international collaboration with Dr. Ronald Micura, from the Leopold-Franzens University (Innsbruck, Austria). Dr. Micura's work is supported by the Fonds zur Forderung der wissenshaftlichen Forschung (FWF) in Austria. A critical aspect of gene expression in all cells is the translation of mRNA templates into specific protein molecules that carry out a broad array of essential life processes. Translation of mRNA is carried out by the ribosome, a two subunit RNA-protein assembly composed of more than fifty individual gene products. Control of gene expression at the level of translation, which is essential to cell survival, can be mediated by numerous mechanisms. The goal of the research is to understand which specific steps in the translation process are affected by the riboswitch response to small-molecule binding. To achieve the goal, the research team will engage a battery of physical and organic chemistry initiatives that will directly image riboswitch-mediated regulation of ribosome-catalyzed translation at the single-molecule scale. In so doing, the team will explore fundamental aspects of the riboswitch regulation mechanism with a special emphasis on the dynamic properties of the system and how such features are regulated by ligand/metabolite binding interactions. The international collaborative research proposed is designed to provide an opportunity for undergraduate, graduate and post-graduate students from distinct research programs to receive interdisciplinary training in organic chemistry and single-molecule fluorescence. This experience will enable the development of new biophysical approaches and experimental techniques for single-molecule research that can be generally applied to the imaging of dynamic life processes at the molecular scale.

这个国际化学合作奖来自国家科学基金会化学部的生命过程化学项目，支持琼和桑福德I号的斯科特·布兰查德博士。康奈尔大学威尔医学院，研究翻译控制机制，其中通常位于信使RNA（mRNA）5 '非翻译区的元件结合小分子代谢物以控制基因表达。这样的元件通常被称为核糖开关结构域。这项工作包括与利奥波德-弗兰茨大学（奥地利因斯布鲁克）的罗纳德米库拉博士进行国际合作。Micura博士的工作得到了奥地利科学研究基金会（FWF）的支持。所有细胞中基因表达的一个关键方面是将mRNA模板翻译成特定的蛋白质分子，这些蛋白质分子执行广泛的基本生命过程。mRNA的翻译是由核糖体进行的，核糖体是由五十多个单独的基因产物组成的两个亚基RNA-蛋白质组装体。在翻译水平上控制基因表达，这对细胞存活至关重要，可以通过许多机制介导。这项研究的目的是了解翻译过程中的哪些具体步骤受到核糖开关对小分子结合的反应的影响。为了实现这一目标，研究小组将开展一系列物理和有机化学举措，这些举措将直接在单分子尺度上对核糖体催化翻译的核糖开关介导的调节进行成像。在这样做的过程中，该团队将探索核糖开关调控机制的基本方面，特别强调系统的动态特性以及这些特征如何通过配体/代谢物结合相互作用进行调控。提出的国际合作研究旨在为来自不同研究项目的本科生，研究生和研究生提供机会，以接受有机化学和单分子荧光的跨学科培训。这一经验将使新的生物物理方法和实验技术的发展，单分子研究，可普遍适用于成像的动态生命过程中的分子尺度。

项目成果

Folding and ligand recognition of the TPP riboswitch aptamer at single-molecule resolution

• DOI: 10.1073/pnas.1218062110
• 发表时间: 2013-03-12
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Haller, Andrea;Altman, Roger B.;Micura, Ronald
• 通讯作者: Micura, Ronald

Tuning a riboswitch response through structural extension of a pseudoknot

• DOI: 10.1073/pnas.1304585110
• 发表时间: 2013-08-27
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Souliere, Marie F.;Altman, Roger B.;Micura, Ronald
• 通讯作者: Micura, Ronald