Postdoctoral Research Fellowships in Biology for FY 2009

这项行动为2009财政年度的NSF博士后研究奖学金提供资金，该奖学金使用2009年美国复苏和再投资法案（公法111-5）的资金。培训和发展计划的标题是“泛素蛋白链如何引发不同的细胞信号”的卡洛斯卡斯塔涅达。这项研究的主办机构是马里兰州大学帕克分校，赞助科学家是大卫富什曼。大的蛋白质通常由结构域组成，它们是蛋白质“模块”，可以独立存在，具有自己的结构和功能。 这些结构域的组合和排列决定了蛋白质功能的多样性。 多聚泛素是这样的蛋白质的一个例子，其由在不同位点连接在一起的泛素蛋白质链组成。 不同连接的多聚泛素链为细胞中的不同事件发出信号，包括蛋白质降解、DNA修复和细胞周期控制。 关于这些链如何在细胞中引发不同的信号，我们知之甚少。 该项目需要对泛素蛋白之间的连接和界面进行修改，然后观察这些变化如何影响多聚泛素链的整体结构和动力学。 定点诱变用于改变接头区的长度和泛素蛋白质之间界面的“粘性”。 实验和计算技术都被用来研究这些链在解决方案中的结构和动态原子分辨率和模型如何这些链响应条件的变化，如pH值。这项研究有助于解决生物物理学中的一个难题：蛋白质结构和动力学如何管理生物功能？ 这个问题影响了基础科学研究的许多领域，包括蛋白质工程、分子建模和生物信息学。 培训目标包括学习蛋白质动力学测量和蛋白质结构测定使用核磁共振，并发展分子建模，分子动力学模拟和基于结构的计算的计算技能。 这项研究与分子生物物理学和生物化学的本科生和研究生的指导紧密结合。

This action funds an NSF Postdoctoral Research Fellowship for FY 2009 using funds from the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). The training and development plan is entitled "How ubiquitin protein chains elicit different cellular signals" for Carlos Castaneda. The host institution for this research is the University of Maryland, College Park, and the sponsoring scientist is David Fushman.Large proteins are commonly comprised of domains, which are protein "modules" that can exist independently with their own structure and function. The combination and arrangement of these domains are responsible for the diversity of protein function. Polyubiquitin is an example of such a protein that is composed of a chain of ubiquitin proteins linked together at distinct sites. Polyubiquitin chains of different linkages signal for different events in the cell, including protein degradation, DNA repair and cell cycle control. Little is known about how these chains evoke different signals in the cell. This project entails making modifications to the linkage and interface between ubiquitin proteins and then observing how these changes affect the overall structure and dynamics of polyubiquitin chains. Site-directed mutagenesis is employed to alter both the length of the linker region and the "stickiness" of the interface between ubiquitin proteins. Both experimental and computational techniques are used to study these chains in solution structurally and dynamically at atomic resolution and to model how these chains respond to changes in conditions, such as pH.This study contributes to addressing a difficult question in biophysics: how do protein structure and dynamics govern biological function? This question impacts many areas of basic science research, including protein engineering, molecular modeling and biological informatics. Training goals include learning protein dynamics measurements and protein structure determination using nuclear magnetic resonance, and developing computational skills in molecular modeling, molecular dynamics simulations and structure-based calculations. This research is tightly integrated with the mentoring of undergraduate and graduate students in molecular biophysics and biochemistry.