NSF Postdoctoral Research Fellowship in Biology

本行动资助美国国家科学基金会2008年度生物学博士后奖学金。该奖学金支持凯文·b·伍德的一项名为“蛋白质-DNA相互作用的物理基础：DNA张力在修饰蛋白质结合中的作用”的研究和培训计划，他将由哈佛大学谢森尼教授主持。蛋白质分子和DNA之间的结合相互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发展许多遗传过程的完整图景至关重要，包括DNA转录和遗传调控。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，并着眼于理解这种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试验对这些模型进行测试，以及继续扩展从单分子数据中提取模型参数的相对年轻的统计方法。由于外部张力可以直接应用于单个DNA分子——无论是在理论上还是在实践中——结合界面对扰动的响应可以定量地进行探测，从而深入了解蛋白质-DNA复合物的潜在物理特性。将严谨的建模与统计数据分析和新颖的实验方法相结合，提供了一种环境，在这种环境中，模型的发展可以受到实验验证的约束，这意味着理论和经验的推力将相互加强和指导。除了研究之外，该研究员还在实验室中积极指导和培训暑期本科生和研究生轮转学生。在一些缺乏研究生水平科学课程的小型本科学院，该研究在科学会议和互动研讨会上进行了展示。数据提取的理论模型和方法将被发布，软件源代码将免费和公开地提供给更广泛的科学界。

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.