CAREER: The Interaction of Ions with DNA: An X-ray Scattering Study

职业：离子与 DNA 的相互作用：X 射线散射研究

• 批准号: 0347220
• 负责人: Lois Pollack
• 金额: $ 52.79万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0347220&HistoricalAwards=false
• 关键词: CAREER; Interaction; Ions; DNA; ray

Two of the most important molecules of life, DNA and RNA, are uniformly negatively charged. Nature takes advantage of the strong interactions between charged particles (e.g., the strong attraction of particles with opposite charges or repulsion of the ones with like charges), to control the shape and function of these nucleic acids. This research project uses x-ray scattering, a newly demonstrated experimental technique, to address fundamental questions about the interaction of positively charged counter-ions with negatively charged nucleic acids. To maintain electrical neutrality in solution, DNA is associated with positively charged partners ranging from small ions to large proteins. Numerous biological processes, including gene regulation and DNA repair, are regulated by the interactions of DNA with charged molecules. These strong interactions are also exploited in the design of pharmaceuticals, small molecules that target and modify DNA. This importance of DNA-charge interactions provides strong motivation for fundamental studies of the properties of these systems. This experimental project is designed to probe these interactions using model DNA systems. This work builds on recent experiments performed at the Cornell High Energy Synchrotron Source in which anomalous small angle x-ray scattering was used to distinguish the scattering signature of a single ionic species (e.g. Rb counterions) from all other atoms/ions in a multi-component system (e.g. DNA in a solution of RbCl). These preliminary measurements enabled unprecedented, quantitative measurements of the spatial distributions of these counterions around the DNA. This project will provide new data to rigorously test conflicting theoretical models of the pertinent interactions. The long-term goal of this project is to exploit this new technology to address biologically relevant questions, such as the role of charged ligands in facilitating attractive forces between DNA strands. This attraction is of fundamental importance to our understanding of how DNA is packaged and stored in our cells. Broader Impacts: This work will have impact in a number of arenas linked together by the theme of promoting interdisciplinary work to a wide audience. The activities range from participation in K-12 outreach through the development of a program to establish a pipeline from predominantly female undergraduate institutions to the Applied Physics graduate program. A successful pilot version of this pipeline program will serve as a model for future efforts. In addition, an Engineering Distribution course will be developed for Cornell undergraduates. The course focuses on interdisciplinary science by introducing important, current topics in molecular biology to students of engineering and physical sciences. Research and Education will be integrated through this course by introducing three new modules. These modules are inspired by the proposed research program and leverage on Cornell's unique research facilities.

生命中最重要的两种分子，DNA和RNA，都带负电荷。 大自然利用带电粒子之间的强相互作用（例如，具有相反电荷的粒子的强吸引力或具有相同电荷的粒子的排斥力），以控制这些核酸的形状和功能。该研究项目使用x射线散射，一种新的实验技术，来解决带正电的反离子与带负电的核酸相互作用的基本问题。为了保持溶液中的电中性，DNA与从小离子到大蛋白质的带正电荷的伙伴相关联。 许多生物过程，包括基因调控和DNA修复，都是通过DNA与带电分子的相互作用来调节的。这些强相互作用也被用于设计药物，靶向和修饰DNA的小分子。DNA-电荷相互作用的这种重要性为这些系统的性质的基础研究提供了强大的动力。该实验项目旨在使用模型DNA系统来探测这些相互作用。这项工作建立在最近的实验中进行的康奈尔高能同步加速器源，其中异常的小角度X射线散射被用来区分散射签名的一个单一的离子物种（如Rb抗衡离子）从所有其他原子/离子的多组分系统（如DNA的RbCl溶液）。这些初步的测量使前所未有的，定量测量这些反离子的空间分布在DNA周围。 该项目将提供新的数据，以严格测试相关相互作用的相互冲突的理论模型。该项目的长期目标是利用这项新技术来解决生物学相关问题，例如带电配体在促进DNA链之间吸引力方面的作用。这种吸引力对于我们理解DNA是如何包装和储存在我们的细胞中至关重要。 更广泛的影响：这项工作将在一些领域产生影响，这些领域通过向广大受众促进跨学科工作的主题联系在一起。 这些活动包括参与K-12外联活动，通过制定一项方案，建立一个从以女性为主的本科院校到应用物理研究生课程的渠道。这一管道方案的成功试点将成为今后努力的典范。 此外，还将为康奈尔大学的本科生开发一门工程分销课程。本课程通过向工程和物理科学的学生介绍分子生物学中重要的当前主题，侧重于跨学科科学。 研究和教育将通过引入三个新模块，通过本课程整合。这些模块的灵感来自拟议的研究计划，并利用康奈尔大学独特的研究设施。