Collaborative Research: Ultra-fast and multiplexed time-resolved hydroxyl radical footprinting of nucleic acids and proteins

合作研究：核酸和蛋白质的超快速、多重时间分辨羟基自由基足迹

• 批准号: 0852796
• 负责人: Michael Brenowitz
• 金额: --
• 依托单位: Yeshiva University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0852796&HistoricalAwards=false
• 关键词: Collaborative; Research; Ultra; fast; multiplexed

Time is linked to cellular function in two important ways. The first way is that the rates of many biological processes determine their function. The second way is that the mechanisms of biological reactions can be revealed by a study of their reaction rates. The goal of this instrument development program is to make tools that efficiently probe the time dependent evolution of biopolymer structures. What is unique about the tools to be built is that they allow reactions to be followed from their earliest steps from the point of view of each monomer of the polymers DNA, RNA and proteins. These tools will be low-cost, easy-to-use and inexpensive-to-operate machines so that biology laboratories will have an entrée into quantitative analysis and biophysical laboratories the incisive tools required for the analysis of very fast biological reactions. The mixing devices that will be built will be able to acquire time ? progress curves commencing from the earliest steps of macromolecular folding and binding reactions with as spatial resolution as fine as every residue of the polymer chain. From a quantitative understanding of the molecular mechanism of individual systems flows a broader understanding of the interrelationships among multiple systems. Ultimately, predictions of the behavior of biological systems based upon the physical properties of their constituent processes will be possible. While such predictions are an admittedly ambitious goal, new technological tools such as those to be built in this study will enable the acquisition of both the depth and breath of information that can make this dream a reality. The project will undergraduates in research through a Summer Undergraduate Research Program. Outreach activities include performing demonstrations is middle and high schools, as well as make them available to middle school and high school teachers.

时间通过两种重要方式与细胞功能相关。第一种方式是许多生物过程的速率决定了它们的功能。第二种方法是通过研究反应速率来揭示生物反应的机制。该仪器开发计划的目标是制造能够有效探测生物聚合物结构随时间变化的工具。即将构建的工具的独特之处在于，它们允许从聚合物 DNA、RNA 和蛋白质的每个单体的角度，从最早的步骤开始跟踪反应。这些工具将是低成本、易于使用且操作费用低廉的机器，因此生物实验室将进入定量分析领域，而生物物理实验室将获得分析非常快的生物反应所需的深入工具。将要建造的混合装置能够获得时间吗？进度曲线从大分子折叠和结合反应的最早步骤开始，其空间分辨率与聚合物链的每个残基一样精细。从对单个系统的分子机制的定量理解出发，可以对多个系统之间的相互关系有更广泛的理解。最终，基于生物系统组成过程的物理特性来预测生物系统的行为将成为可能。虽然这样的预测无疑是一个雄心勃勃的目标，但新技术工具（例如本研究中构建的工具）将能够获取深度和气息的信息，从而使这一梦想成为现实。该项目将通过暑期本科生研究计划让本科生进行研究。外展活动包括在初中和高中进行演示，以及向初中和高中教师提供演示。