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

时间与细胞功能有两个重要的联系。第一种方法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生物反应的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有效探测生物聚合物结构随时间变化的工具。要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，从最初的步骤跟踪反应。这些工具将是低成本、易于使用和操作成本低廉的机器，因此生物实验室将有机会进行定量分析，生物物理实验室将成为分析非常快速的生物反应所需的敏锐工具。将要建造的混合装置能够获得时间吗？从大分子折叠和结合反应的最早步骤开始的进展曲线，其空间分辨率精细到聚合物链的每个残留物。从对单个系统的分子机制的定量理解中，可以更广泛地理解多个系统之间的相互关系。最终，基于生物系统组成过程的物理特性来预测其行为将成为可能。虽然这样的预测是一个公认的雄心勃勃的目标，但新的技术工具，如在这项研究中建立的工具，将使我们能够获得深度和呼吸的信息，使这一梦想成为现实。该项目将本科生通过暑期本科生研究计划进行研究。外展活动包括在初中和高中进行示范，并向初中和高中教师提供示范。

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.