Mechanisms and Regulation of Cell Division

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Cell division is a highly coordinated set of events that ensures the faithful transmission of genetic material from one mother cell to two newly formed daughter cells. The mitotic spindle is the complex molecular machine used by the cell to separate the genetic material. However, the assembly and regulation of the mitotic apparatus is still incompletely understood. This project will increase this understanding by elucidating the role and mechanism of function of five enzymes whose roles in mitosis have not been previously appreciated. This project will have a Broader Impact for society by training and preparing the next generation of scientists for careers in STEM fields. A diverse group of students at all levels, from high school through graduate students, will participate in educational, mentoring, and research training activities. This research will enable students to become independent critical thinkers, to generate scientific data, and to develop computational software that will be freely available and will benefit the scientific community. All research results will be disseminated to a broad audience through publications, research presentations, and at science outreach events. The mitotic spindle, comprised largely of microtubules, is key to the process of cell division. It's proper assembly, function, and regulation relies on a multitude of enzymatic reactions and protein-protein interactions that are tightly controlled in a spatial and temporal manner. Current efforts to comprehend cell division as a biological system have been hampered by a lack of understanding of the enzymatic machinery and their mechanistic functions that contribute to cell division. This proposal integrates experimental and computational approaches in a synergistic fashion to address these gaps in knowledge. Many enzymes with uncharacterized roles in cell division were recently uncovered in a proteomic screen to identify novel mitotic microtubule associated proteins. Genetic screens confirmed the importance of these proteins for cell division. These were termed novel cell division proteins (NCDPs). To further elucidate the mechanisms that drive and regulate cell division, this project will characterize the function of five NCDPs using a range of cell biological, molecular, and genetic, and biochemical approaches to determine their localization, function and mode of regulation in cell division. This project will develop novel computational tools to analyze NCDP proteomic data sets, and establish a user-friendly open access web server that the scientific community can use to analyze mass spectrometry data. Together, this research will advance an understanding of the enzymatic activities that drive and regulate cell division.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.