A hallmark of successful cell division is the accurate segregation of chromosomes to daughter cells during mitosis and meiosis. Understanding how cells mediate this critical event is central to understanding genome stability and, conversely, how its failure contributes to genetic abnormalities in cells and organisms. The centromere is a specialized structure present on all chromosomes that is absolutely essential for chromosome segregation because it provides the physical location for chromosomes to attach to spindle microtubules and be distributed equally to daughter cells. Even though a large number of centromeric components have been identified to date, particularly in humans, only a subset can be identified in the genome of Drosophila melanogaster. Furthermore, increasing new evidence suggests that the centromeres of Drosophila are regulated differently from those of the other eukaryotes analyzed so far. This raises the important question of whether pathways responsible for centromere function are conserved among different organisms. Characterizing this process in Drosophila, a model system that offers powerful cell biology and genetics, will ultimately contribute to a comparative understanding of centromere biology that will provide further insights into this fundamental phenomenon across species. Specifically, this project will identify novel components involved in centromere structure and function and define their role in pathways that mediate maintenance of the centromere through multiple cell divisions. In addition, an exciting new role for the cell cycle in regulating these processes will be further investigated. These goals will be achieved using an alliance of cell biological, molecular and biochemical methodologies to fill major gaps in our knowledge of the intriguing world of chromosome biology.
Broader Impacts: This project includes ample opportunities for collaborative research exposing undergraduate and graduate students to the interdisciplinary nature of modern scientific investigation. An additional educational goal is to establish a comprehensive hands-on module that exposes students to cutting-edge cell division research including the latest methods in timelapse microscopy. Key outreach efforts are the promulgation of visual tools for the dissemination of knowledge about chromosome segregation and cell division to middle and high school students, teachers and the general public; the participation in initiatives to attract and develop the next generation of female scientists; and the involvement in programs exposing high school students to laboratory research.
