International Collaboration in Chemistry: Single-molecule FRET

美国国家科学基金会化学分部生命过程化学项目的国际化学合作奖支持康奈尔大学琼和桑福德·i·威尔医学院的斯科特·布兰查德博士研究翻译控制机制，即信使RNA (mRNA) 5'-非翻译区中的元素结合小分子代谢物来控制基因表达。这些元素通常被称为核糖开关结构域。这项工作包括与利奥波德-弗兰岑斯大学（奥地利因斯布鲁克）的Ronald Micura博士的国际合作。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mRNA模板翻译成特定的蛋白质分子，这些蛋白质分子执行一系列基本的生命过程。mRNA的翻译是由核糖体进行的，核糖体是由50多个单独的基因产物组成的两个亚基rna -蛋白质组装体。翻译水平上的基因表达控制对细胞存活至关重要，可以通过多种机制介导。该研究的目的是了解翻译过程中的哪些特定步骤受到小分子结合的核糖开关反应的影响。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活动，直接在单分子尺度上成像核糖体介导的核糖体催化翻译调节。在此过程中，该团队将探索核糖体开关调节机制的基本方面，特别强调系统的动态特性以及配体/代谢物结合相互作用如何调节这些特征。该国际合作研究计划旨在为来自不同研究项目的本科生、研究生和研究生提供一个机会，让他们在有机化学和单分子荧光领域接受跨学科的培训。这一经验将有助于开发新的生物物理方法和单分子研究的实验技术，这些方法和技术可以普遍应用于分子尺度上动态生命过程的成像。

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.