Model studies of chromosome structure and dynamics

生物学的一个中心问题是真核生物基因组中编码的信息是如何包装和解码的。这项研究的目的是提供一个更好的了解真核细胞染色体的结构，以及染色体结构如何影响基因组功能。一个更广泛的成果将是开发公共领域的教育软件，学生可以在互联网上免费获得。该软件是教授蛋白质和核酸结构和功能原理的教科书的替代品，并有可能改变高中和大学教授这些主题的方式。此外，还将对博士后、博士、本科生进行研究原理和基础知识的培训。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之间的关系。模型染色体将在体外由纯蛋白质和DNA组分组装，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-末端尾部结构域、核小体酸性补丁、接头DNA和染色体蛋白质。为了获得这些信息，该研究将采用广泛的实验工具箱，包括荧光显微镜测量染色体形状，分析超浓缩测量染色体大小，以及光漂白后的荧光恢复测量核小体-核小体包装动力学。该研究预计将产生数据，以支持一个新的，变革性的模型间期染色体结构和dynamics.This奖项反映了美国国家科学基金会的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.