NSF Postdoctoral Research Fellowship in Biology

这一行动为NSF 2008财年生物学博士后奖学金提供了资金。该奖学金支持一项名为《蛋白质-DNA相互作用的物理基础：DNA张力在修改蛋白质结合中的作用》的研究和培训计划，该计划将由哈佛大学谢孙尼教授主持。蛋白质分子和DNA之间的结合作用构成了许多分子生物学的基础。对结合的定量物理理解对于建立包括DNA转录和遗传调控在内的许多遗传过程的完整图景至关重要。在这个项目中，理论和实验技术的结合被用来描述蛋白质与DNA的结合，着眼于了解结合如何被外力改变。该项目的具体目标包括开发力调节蛋白质与DNA结合的一般物理模型，使用基于荧光的单分子结合分析对这些模型进行测试，以及继续扩展仍然相对年轻的从单分子数据中提取模型参数的统计方法。由于外加张力可以直接作用于单个DNA分子--无论是在理论上还是在实践中--结合界面对扰动的反应可以进行定量探索，从而深入了解蛋白质-DNA复合体的潜在物理机制。严格的建模、统计数据分析和一种新颖的实验方法的综合提供了一种环境，在这种环境中，模型的开发可以受到实验验证的限制，这意味着理论和经验的推进将相互促进和指导。除了研究，这位研究员还在实验室指导和培训暑期本科生和毕业生轮换学生方面发挥积极作用。这项研究在科学会议和几个缺乏研究生水平科学课程的小型本科生学院的互动研讨会上展示。将出版数据提取的理论模型和方法，并向更广泛的科学界免费和公开提供软件源代码。

This action funds an NSF Postdoctoral Fellowship in Biology for FY 2008. The fellowship supports a research and training plan entitled "Physical Underpinnings of Protein-DNA Interactions: The Role of DNA Tension in Modifying Protein Binding" for Kevin B. Wood who will be hosted by Prof. Sunney Xie at Harvard University. Binding interactions between protein molecules and DNA form the basis for much of molecular biology. A quantitative physical understanding of binding is crucial for developing a complete picture of many genetic processes, including DNA transcription and genetic regulation. In this project, a combination of theoretical and experimental techniques are being employed to characterize the binding of proteins to DNA, with an eye towards understanding how binding can be modified by external forces. Specific goals of the project include the development of general physical models of force-modulated protein binding to DNA, the testing of these models using a fluorescence-based single molecule binding assay, and the continued expansion of the still relatively young statistical approaches for extracting model parameters from single molecule data. Because external tension can be directly applied to single DNA molecules--both in theory and practice-- the response of the binding interface to perturbation can be quantitatively probed, lending insight into the underlying physics of the protein-DNA complex. The synthesis of rigorous modeling with statistical data analysis and a novel experimental approach provides a setting in which model development can be constrained by experimental validation, meaning that the theoretical and empirical thrusts will mutually reinforce and guide one another. In addition to research, the Fellow is taking an active role in mentoring and training summer undergraduate students and graduate rotation students in the lab. The research is presented at scientific meetings and also during interactive seminars at several small undergraduate colleges which lack graduate level science programs. The theoretical models and methods of data extraction will be published, with software source code freely and openly available to the wider science community.