Analysis of RNA-metal ion interactions by solution Raman spectroscopy

有了这个奖项，生命过程计划的化学支持凯斯西储大学RNA中心的Michael Harris教授的研究，开发同位素编辑的拉曼光谱作为一种新的生物物理工具，用于研究与RNA骨架磷酸氧相关的金属离子。 金属离子结合必然改变相邻磷酰氧的化学环境，导致拉曼光谱的变化。 拉曼光谱中的特征信号又可以提供关于金属缔合的性质和位置的有价值的信息。 通过同位素编辑，这些研究应该允许在单个磷酸盐的水平上对溶液中的特定金属-RNA相互作用进行实验性询问。 所获得的信息的定量性质使其直接适用于正在开发的计算模型，以描述RNA-金属离子结合的结构和能量。该项目的更广泛的影响将包括基于同位素标记（生物有机化学）和拉曼光谱（生物物理化学）相结合的化学生物学新工具的开发。 这里的成功可能会转化为该技术在生物物理化学中的更广泛应用。 PI将高级本科生纳入研究团队，特别强调传统上代表性不足的科学群体的成员。 学生将有最先进的仪器设备的实践经验，并通过小组学习练习参与数据分析。因此，该项目的一个重要组成部分是将研究目标纳入教育，为下一代科学家和工程师提供培训机会。该研究项目由NSF BIO董事会分子和细胞生物科学（MCB）部门的生物分子动力学，结构和功能集群共同资助。

With this award, the Chemistry of Life Processes Program is supporting the research of Professor Michael Harris of the RNA Center at Case Western Reserve University to develop isotope-edited Raman spectroscopy as a new biophysical tool for the study of metal ions associated with backbone phosphate oxygens of RNA. Metal ion binding necessarily changes the chemical environment of neighboring phosphoryl oxygens, resulting in changes in the Raman spectrum. Signature signals in the Raman spectrum can in turn provide valuable information on the nature and position of the metal association. With isotope editing, these studies should allow for the experimental interrogation of specific metal-RNA interactions in solution, at the level of individual phosphates. The quantitative nature of the information gained makes it directly applicable to computational models being developed to describe the structure and energetics of RNA-metal ion binding.The Broader Impacts of the project will include the development of new tools for chemical biology based upon a combination of isotope-labeling (bioorganic chemistry) and Raman spectroscopy (biophysical chemistry). Success here may translate to broader applications of the technique in biophysical chemistry. The PI will incorporate advanced undergraduates into the research team, with a special emphasis on members of traditionally underrepresented groups in science. Student will have hands-on experience with state of the art instrumentation and participate in data analysis facilitated through small group learning exercises. Thus, an important component of the project is the integration of the research goals into education, providing a training opportunity for the next generation of scientists and engineers.This research project is being co-funded by the Biomolecular Dynamics, Structure and Function Cluster within the Molecular and Cellular Biosciences (MCB) Division of the BIO Directorate at NSF.