This research will take an evolutionary approach to understand how centromeres assemble. Centromeres are essential elements of chromosomes that are crucial for proper transmission of genetic information from cell to cell during cell division. When centromeres fail to assemble correctly, the result can be an imbalance in chromosome number whereby cells have too many or too few chromosomes. In animals, such an imbalance can lead to visible developmental defects, which in turn can lead to birth defects or death. This study aims to impact our understanding of the conserved aspects of centromere assembly, and hence aspects that are crucial for preventing an imbalance in chromosome number and catastrophic developmental defects. In addition, this research will have a strong educational impact by providing opportunities for undergraduate and graduate students to engage directly in research and by developing a new hands-on summer laboratory workshop for high school teachers to enable them to learn about chromosome biology and take the lessons learned back to their high school classrooms.
In eukaryotes, centromeres assemble by binding special centromere-specific histone H3 proteins, which are escorted to the correct location on the chromosome by chaperone proteins. Recent results have revealed structural and sequence variation in these chaperones, which suggests that during evolution, multiple mechanisms may have arisen for assembling centromeres. This work will focus on analysis of the chaperone proteins using evolutionary, structural and functional studies. Comparisons will be made among a newly discovered chaperone from Drosophila and two well-conserved chaperones from yeast and mouse. The outcomes of the work will provide unique mechanistic and evolutionary insights into the fundamental processes that govern centromere structure and function. The project will also have broad impact from the educational perspective. The research will be carried out by undergraduate and graduate students, many of whom are women, thereby providing opportunities for scientific training, career development and direct participation in the promulgation of scientific findings through publications and conference presentations. In addition, a novel hands-on summer laboratory workshop will be developed for high school teachers (ten per year), focusing on the basic biology of chromosome segregation and cell division and extending to emerging topics such as stem cells and altered genetic states in cancer. The teachers will leave the workshop armed with teaching materials, ideas for lesson plans, and positive research experiences through their direct involvement in experimentation. By enabling the teachers to take what they learn back to their classrooms, the workshops will have a multiplier effect on the scientific education of scores of pre-college level students.