Model studies of chromosome structure and dynamics

生物学中的一个核心问题是真核生物基因组中编码的信息如何被打包和解码。本研究的目的是提供对真核生物染色体结构的更好理解，以及染色体结构如何影响基因组功能。更广泛的结果将是开发公共领域的教育软件，这些软件将通过互联网免费提供给学生。这款软件代表了蛋白质和核酸结构与功能原理教学的一种替代教材，并有可能改变这些主题在高中和大学水平的教学方式。此外，该项目还将为博士后、博士和本科生提供研究原则和基础方面的培训。本研究旨在了解体外染色质纤维动力学与体内间期染色体结构的关系。模型染色体将由纯蛋白质和DNA组分在体外组装，并用于确定指定染色体结构和核小体-核小体包装的因素，包括核心组蛋白n端尾结构域、核小体酸性斑块、连接体DNA和染色体蛋白质。为了获得这些信息，该研究将使用广泛的实验工具箱，包括荧光显微镜测量染色体形状，分析性超离心测量染色体大小，光漂白后荧光恢复测量核小体-核小体包装动力学。该研究有望产生数据，以支持一种新的，过渡性的间期染色体结构和动力学模型。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

A central question in biology is how the information encoded in a eukaryotic genome is packaged and decoded. The goal of this research is to provide an improved understanding of the structure of a eukaryotic chromosome, and how chromosome structure influences genomic function. A broader outcome will be development of public-domain educational software that will be freely available students over the internet. This software represents an alternative to textbooks for teaching the principles of protein and nucleic acid structure and function, and has the potential to transform the way these topics are taught at the high school and college level. In addition, the project will provide training in research principles and fundamentals at the post-doctoral, doctoral, and undergraduate levels.This research aims to understand the relationship between chromatin fiber dynamics in vitro and interphase chromosome structure in vivo. Model chromosomes will be assembled in vitro from pure protein and DNA components and used to determine the factors that specify chromosome structure and nucleosome-nucleosome packaging, including the core histone N-terminal tail domains, the nucleosome acidic patch, linker DNA, and chromosomal proteins. To obtain this information, the research will employ a broad experimental toolbox, including fluorescence microscopy to measure chromosome shape, analytical ultracentrifugation to measure chromosome size, and fluorescence recovery after photobleaching to measure nucleosome-nucleosome packaging dynamics. The research is expected to yield data in support of a new, transformative model of interphase chromosome structure and dynamics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.