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

时间通过两种重要方式与细胞功能联系在一起。第一种方式是，许多生物过程的速率决定了它们的功能。第二种方法是通过对生物反应速率的研究来揭示生物反应的机理。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。将要制造的工具的独特之处在于，从聚合物DNA、RNA和蛋白质的每个单体的角度来看，它们允许从最早的步骤开始进行反应。这些工具将是低成本、易使用和操作廉价的机器，这样生物实验室就可以进入定量分析和生物物理实验室，这些实验室是分析非常快速的生物反应所需的尖端工具。将要建造的混合设备将能够获得时间吗？从大分子折叠和结合反应的最早步骤开始的进度曲线，空间分辨率与聚合物链上的每个残基一样精细。通过对单个系统的分子机制的定量了解，可以更广泛地了解多个系统之间的相互关系。最终，根据生物系统组成过程的物理性质来预测生物系统的行为将成为可能。诚然，这样的预测是一个雄心勃勃的目标，但新的技术工具，如本研究中将要建立的工具，将使我们能够获得使这一梦想成为现实的信息的深度和广度。该项目将通过暑期本科生研究计划在本科生中进行研究。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.