Mechanism of Condensins and Cohesins

智力优势：所有活细胞的染色体都折叠成一个高度有序的结构，具有多层次的组织，以适应一个有限的空间。为了支持细胞功能，染色体结构在全局和局部水平上都经历了各种变化。理解整体染色质组织尤其具有挑战性，因为它需要解释染色体蛋白如何控制更大的染色体的结构。这个项目的重点是被称为凝聚蛋白和内聚蛋白的蛋白质的机制，它们在从细菌到人类的生物体中染色体的整体包装中起着核心作用。在本项目中，将探索几种这样的蛋白质复合物的DNA组织机制，包括细菌凝缩蛋白MukBEF和真核凝缩蛋白和内聚蛋白。该项目涉及使用几种互补技术来评估体外、活细胞和单个DNA分子中的DNA重构，并包括开发适合于高阶染色质结构的生化解剖方法。这项研究的完成将揭示染色质重排的机制，并将增加我们操纵染色质结构的能力。更广泛的影响：这个项目的更广泛的影响包括建立一个纳米操作研究中心，专门研究物理、化学和生物的界面问题，以及研究生和本科生水平的综合跨学科教育。磁镊子是一种允许在单个分子水平上分析DNA结构的技术，它对生物学问题的关注将与俄克拉何马州纳米网络中现有的和新兴的纳米技术研究协同作用。教育部分包括让研究生和本科生接触到自组织系统的单分子研究，以及在研究生和本科生层面开发生物物理化学的新课程。

INTELLECTUAL MERIT: Chromosomes of all living cells are folded into a highly ordered structure with multilevel organization to fit within a confined space. To support cellular functions, chromosome structure undergoes a variety of changes both on the global and local levels. Understanding global chromatin organization is particularly challenging because it requires explaining how chromosomal proteins control the structure of the much bigger chromosome. This project focuses on the mechanism of proteins called condensins and cohesins, which play a central role in global packing of the chromosomes in organisms ranging from bacteria to humans. In this project, the mechanism of DNA organization by several such protein complexes, including the bacterial condensin named MukBEF and the eukaryotic condensins and cohesins, will be explored. The project involves the use of several complementary techniques that assess DNA reconfiguration in vitro, in live cells, and on a single DNA molecule and includes the development of methods suitable for biochemical dissection of the higher order chromatin structure. The completion of this study will uncover the mechanism of chromatin rearrangements by condensins and cohesins and will increase our ability to manipulate chromatin structure.BROADER IMPACT: The broader impact of this project includes the establishment of a nanomanipulations research center specializing in problems at the interface of physics, chemistry and biology as well as integrated interdisciplinary education on graduate and undergraduate levels. The magnetic tweezers, a technology that allows for analysis of DNA configuration at the level of a single molecule, and its focus on biological problems will be synergistic to the existing and emerging nanotechnology research within the Oklahoma NanoNet. The educational component includes the exposure of graduate and undergraduate students to single molecule research on self-organizing systems and the development of new courses in biophysical chemistry both on graduate and undergraduate levels.