CAREER: Structure, Dynamics, and Function of the Packaging RNA Studied using Site-directed Spin Labeling

职业：使用定点自旋标记研究包装 RNA 的结构、动力学和功能

• 批准号: 0546529
• 负责人: Peter Qin
• 金额: $ 66.57万
• 依托单位: University of Southern California
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0546529&HistoricalAwards=false
• 关键词: CAREER; Structure; Dynamics; Function; Packaging

Nucleic acids are essential in biological processes, and information on nucleic acids structure and conformational changes is critical in understanding their functions. This project will establish a new method for investigating nucleic acids conformations. The method is based on the site-directed spin labeling (SDSL) technique, where structural and dynamic information is derived from a stable nitroxide radical attached at a specific site of a macro-molecule. The research will explore a nitroxide probe that can be attached, in an efficient and cost-effective manner, to arbitrary nucleic acid sequences. Nanometer distances between a pair of such nitroxides will be measured, and the resulting data will be utilized to map the global structures of nucleic acids. To demonstrate the SDSL methods, global structures of nucleic acid molecules without prior known high-resolution structures will be studied. These include the packaging RNA that plays an essential role in the strongest bio-molecular motor known today : the phi29 DNA packaging motor. The studies will set a precedent for a wide range of SDSL studies on nucleic acids and nucleic acid/protein complexes without prior high-resolution structures. Broader Impacts: The PI will establish innovative, inter-disciplinary programs that integrate research and teaching at both the undergraduate and graduate level. A new general education course, called "Genes, Life, and Society", will be developed. The course will present the nature of genes with rigorous and precise molecular descriptions of nucleic acids structure and function, and will link the scientific concepts with contemporary societal issues such as evolution and diversity of our society. The course will utilize "BioSIGHT", a multi-media teaching platform being developed at an NSF-funded center at USC. The class will target a large population of science and non-science students, and will be used in outreach programs to high-school teachers through public lectures and web sites.

核酸在生物过程中是必不可少的，有关核酸结构和构象变化的信息对于理解其功能至关重要。该项目将建立一种研究核酸构象的新方法。该方法基于位置定向自旋标记(SDSL)技术，其中结构和动态信息来自于连接在大分子特定位置的稳定的氮氧自由基。这项研究将探索一种可以高效且经济实惠地连接到任意核酸序列上的氮氧化物探针。一对这样的氮氧化物之间的纳米距离将被测量，产生的数据将被用来绘制核酸的全球结构图。为了演示SDSL方法，我们将研究没有已知高分辨率结构的核酸分子的全局结构。其中包括包装RNA，它在当今已知的最强大的生物分子马达：phi29 DNA包装马达中发挥着至关重要的作用。这些研究将为在没有先前高分辨率结构的情况下对核酸和核酸/蛋白质复合体进行广泛的SDSL研究开创先例。更广泛的影响：PI将建立创新的、跨学科的课程，将本科生和研究生的研究和教学结合起来。将开发一门新的通识教育课程，名为“基因、生命和社会”。本课程将介绍基因的性质，以及对核酸结构和功能的严格和精确的分子描述，并将科学概念与当代社会问题(如我们社会的进化和多样性)联系起来。该课程将使用“BioSIGHT”，这是一个由南加州大学国家科学基金会资助的中心开发的多媒体教学平台。该课程将面向大量的理科和非理科学生，并将用于通过公共讲座和网站向高中教师推广的计划。