Model studies of chromosome structure and dynamics

Colorado State University, Fort Collins CO

Investigators

Abstract

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.