Micromechanical Analysis of Chromosome Structure

Northwestern University, Evanston IL

Investigators

Abstract

Chromosomes directly control the growth and development of all living organisms, using genetic information stored in the structure of their DNA. The DNA molecules in human chromosomes are more than a centimeter long, or roughly 1000 times longer than the cells in which they are found, yet they must be precisely replicated and then the duplicates separated from one another, in order for daughter cells resulting from each cell division to have a complete set of genes. The process of chromosome segregation is crucially dependent on their overall structure, which is dramatically changed during cell division: as cells prepare to divide, their chromosomes change from an unfolded state to compact, tightly folded cylindrical structures. This project is aimed at understanding how chromosomes are folded into this "mitotic" form occurring during cell division, and will provide, for the first time, direct study of forces provided by interactions between the specific molecules responsible for folding of the chromosome. A unique technology will be used to probe the strength of interactions between molecules inside chromosomes: individual chromosomes will be removed from dividing cells, and then their mechanical properties will be directly measured, using tiny (micron-scale) force-measuring probes. This project will seek to study the functions of specific molecules in the folding of chromosomes during cell division. By suppressing production of specific proteins and then observing changes in the mechanical properties and overall folding of mitotic chromosomes, the roles of those specific proteins in holding the chromosome together will be determined. Also, this project will use the same approach to determine the relative strength of folding of different parts of chromosomes, and also establish methods to study the mechanics of chromosomes between cell divisions. Broader Impacts: This project will achieve broad impact through novel experiments on the open questions concerning large-scale chromosome structure. The general problem of regulation of structure and topology of large polymers is of interest to a highly interdisciplinary audience of biologists, physicists, materials scientists, chemists and engineers. This interdisciplinary research at the interface between biology and physics will train graduate students in quantitative biology, an area in which junior faculty is in heavy demand by universities. Broader impacts will also be achieved by providing research experience to high school and undergraduate students who otherwise might not have access to university-level scientific research. Priority will be given to filling research positions at all levels with women and members of underrepresented minority groups.