Periodic Reporting for period 1 - ChromoDrive (Investigating how anaphase chromosomal motion is generated during mitosis and meiosis)
Reporting period: 2017-07-01 to 2019-06-30
The phase of cell division during which the chromosomes are physically separated is called anaphase. Although anaphase has fascinated generations of scientists for more than a century, the mechanisms that underlie the poleward movement of the chromosomes in mammals are still unclear. Several studies have suggested candidate proteins that may power their movement, however there were no conclusive results due to the technically challenging nature of this research. The main reason for this challenge is that one must efficiently inactivate the candidate protein(s) only at the onset of anaphase so as to avoid disrupting the previous phases of cell division, which could confound the results.
Technologies to rapidly inactivate proteins of interest have recently become available. Here, we proposed to use these techniques to systematically dissect the mechanism(s) underlying poleward chromosome movement during anaphase in both mammalian germ cells (oocytes, meiosis) and non-transformed mammalian somatic cells (mitosis) in order to understand how chromosomes are separated during anaphase.
We characterised these movements by depleting candidate proteins and using drugs to acutely inhibit targets to investigate how these movements are controlled in the cell. We found several proteins which govern these oscillations, as well as the overall movement of chromosomes towards the poles, and are continuing to investigate how these proteins generate the force to move chromosomes towards the poles.
Our results have helped to understand what happens during anaphase and how chromosomes move towards the spindle poles. We have found several proteins which control this process, which have the potential to be used as therapeutic targets in fertility treatment and diseases such as cancer. For example, we may be able to target these proteins to cause a catastrophic anaphase, thereby pushing cancer cells to die by apoptosis. Conversely, we may be able to understand if these proteins are affected in the eggs of older women, and find treatments to improve the fidelity of chromosome segregation.