The role of microtubule regulators in the progression of cancer: investigating the link between BRCA2 and depolymerising kinesins.

The mitotic kinesin KIF2C/MCAK regulates microtubule length in the mitotic spindle and plays a role in preventing chromosome-microtubule attachment errors. MCAK is overexpressed in several cancers and elevated expression correlates with increased metastasis and poor patient prognosis. However, the mechanistic link between dysregulation of MCAK expression and cancer progression is currently unknown.

MCAK has recently been discovered to interact with the BRCA2 tumour suppressor protein. Mutations in BRCA2 are associated with several cancers, including breast, ovarian and prostate cancers. BRCA2 is known to be essential for double-strand DNA break repair in mitosis and meiosis. However, interaction with MCAK suggests a previously unknown and unexpected role for BRCA2 in alignment of chromosomes in metaphase.

This project will uncover the impact of interaction with BRCA2 on the activity of MCAK and how this effects the role of MCAK in chromosome segregation and cancer progression. The overall aim is to uncover the mechanistic link between dysregulation of microtubule dynamics and cancer progression.

The work will use advanced fluorescence microscopy techniques to observe and quantify microtubule dynamics and the impact of MCAK and BRCA2.

The project is a collaboration with the Université Paris-Saclay, France. There is scope to work on this project as a PhD or an MRes project duration.