Model studies of chromosome structure and dynamics

染色体结构和动力学的模型研究

• 批准号: 1814012
• 负责人: Jeffrey Hansen
• 金额: $ 75.57万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1814012&HistoricalAwards=false
• 关键词: Model; studies; chromosome; structure; dynamics

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.

生物学中的一个中心问题是，真核生物基因组中编码的信息是如何打包和解码的。这项研究的目的是为了更好地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。一个更广泛的结果将是开发公共领域的教育软件，学生可以通过互联网免费获得这些软件。该软件代表了教授蛋白质和核酸结构和功能原理的教科书的另一种选择，并有可能改变高中和大学水平上这些主题的教学方式。此外，该项目将提供博士后、博士和本科生水平的研究原理和基础方面的培训。这项研究旨在了解体外染色质纤维动力学和体内间期染色体结构之间的关系。模型染色体将由纯蛋白质和DNA组分在体外组装，并用于确定决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末端尾区、核小体酸性斑块、连接物DNA和染色体蛋白。为了获得这些信息，这项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，分析性超速离心法测量染色体大小，以及光漂白后的荧光恢复来测量核小体-核小体包装动力学。这项研究预计将产生支持间期染色体结构和动力学的新的变革性模型的数据。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Silencing the genome with linker histones

用连接组蛋白沉默基因组

• DOI: 10.1073/pnas.2009513117
• 发表时间: 2020
• 期刊: Proceedings of the National Academy of Sciences
• 作者: Hansen, Jeffrey C.