Kinesin Holo-complexes in Mitosis
Mitosis is a highly regulated process that allows equal distribution of the genetic material to the daughter cells. The mitotic spindle is a bipolar structure composed of highly dynamic microtubule polymers. The formation and maintenance of the bipolar spindle, kinetochore-microtubule attachments, chromosome movement and microtubule dynamics during mitosis are critical to maintaining genomic integrity. Several of the mitotic microtubule-associated proteins are key to controlling these processes and therefore prime candidates as anti-cancer drug targets.
Our goals are to determine how the key mitotic players that contribute to correct chromosome segregation are controlled to align chromosomes and biorient kinetochores so efficiently, and the molecular principles that govern the progression of mitosis. Aneuploidy and chromosome instability can arise from defects in chromosome segregation and are a hallmark of cancer. Therefore, mitotic molecular motors and other microtubule-associated proteins that control spindle assembly and chromosome segregation represent key cancer drug targets to be further evaluated.
Using biochemistry and structural biology, we study the architecture of cell cycle complexes, while cell biology approaches give us a cellular context to understand how molecular machines work. We have already published exciting insights into mechanisms and regulation of mitotic microtubule-associated protein complexes using combined structural, biochemical, and cell biological approaches.
Principal Investigator, CRUK Career Development Fellow and UoE Senior Research Fellow
|Thibault Legal||Research Assistant/PhD student|
|Jovana Deretic||Darwin Trust Graduate Student|
Cancer, Mitosis, Kinesin, Chromosome Segregation, Mitotic Microtubule-Associated Protein
Structural, Biochemical, Cell biology, Imaging