Mechanomolecular regulation of cell division

PROJECT SUMMARY Cell division is a physical process when the genome - distributed across the replicated chromosomes - is equally separated prior to cleavage into two daughter cells. Given its central importance to life, integrated physical and biochemical fail-safe mechanisms have evolved to make cell division a high-fidelity process. However, natural selection does not yield perfection and failures in cell division result in aneuploidy, which causes a majority of miscarriages in the first trimester, birth defects, and has been implicated in tumorigenesis and cancer metastasis. Our long-term goal is to characterize fundamental and conserved mechano-molecular mechanisms of cell divi- sion. In the proposed work, we will combine advanced live-cell imaging approaches with molecular and biochem- ical methods to advance two areas of inquiry central to successful cell division. First, we will investigate the functional contributions of extremely large intrinsically disordered regions (ELIDRs) in proteins at the kinetochore and perichromosomal layer. Second, we will study how a phenomenon called branching microtubule nucleation is regulated to promote efficient and timely capture of chromosomes by spindle microtubules. A more compre- hensive understanding of how the complex biological processes of cell division are orchestrated by mechanical and biochemical pathways will be foundational to treating diseases stemming from improper cell division.