First funding for new group leader Maxim Igaev

Maxim joined the Division of Computational Biology in the School of Life Sciences in October last year from the Max Planck Institute for Multidisciplinary Sciences (Göttingen, Germany). This first funding award will allow Maxim to use a computational approach to understand kinetochore-mediated force generation by microtubules in chromosome segregation. 

Our body consists of approximately 60 trillion cells. The integrity and functionality of our tissues and organs rely on a proper control of cell division and the underlying cell cycle. In cancer cells, however, the division process is out of control: the “accelerators” and “brakes” of the cell cycle are broken. When these controls do not operate properly, the normal regulation of cell division fails, leading to uncontrolled growth and spread of cancer cells. 

A critical aspect of cell division involves the precise separation of pairs of sister chromosomes. To do this, tiny filaments called microtubules interact with molecular structures located on each chromosome pair called kinetochores, and these filaments then pull the sister chromosomes apart. These attachments must be strong and precise to ensure healthy cell division. However, at present it is not fully known how kinetochores and microtubules interact, especially under the separation forces involved in cell division. 

The research supported by the AMS Springboard award aims to uncover how kinetochores and microtubules work together to ensure accurate chromosome segregation. Using advanced computer simulations and collaborating with the leading experimental labs of Professor David Barford (MRC LMB, Cambridge), Professor Rastko Sknepnek (UoD SLS, Dundee), and Professor Tomoyuki Tanaka (UoD SLS, Dundee), they will create detailed computational models of this interaction. Specifically, they will reveal how these structures maintain their connection under the forces involved in cell division and how errors in this process might be corrected. By understanding this process better, they aim to discover new ways to target and disrupt the erroneous kinetochore-microtubule attachments in cancer cells, leading to more effective and selective therapies.