Mechanisms for new microtubule nucleation in the mitotic spindle

Accurate cell division is essential for life in all eukaryotes. During development, we start life as a single cell and become large assemblies made of ~40 trillion cells, and this process of cell division continues into adult life to replenish dead cells. Errors in this process can lead to cell death, cancer or birth defects. Cell division involves the accurate segregation of genetic material between the two resulting daughter cells. This is achieved by the formation of a bipolar mitotic spindle, composed of thousands of microtubules (MTs) and their associated proteins which, in concert with different motors and non-motor proteins facilitates sister chromatid separation. Each chromosome is connected to the mitotic spindle via its kinetochore, a protein disc with ~20 microtubules attached to it forming a kinetochore fibre (K-fibre). Recent research has found that in human cells K-fibres are held together by interconnecting proteins termed the 'mesh'. These proteins appear to organise the microtubules within the K-fibre and provide stability to ensure accurate cell division. The aim of my PhD is to investigate the role of TACC3, a previously identified component of the 'mesh', within the mitotic spindle. In particular, I will investigate the potential phase separated structure of this protein in gene edited human cells lines using a variety of microscopy techniques. I will also test whether TACC3 is a site for new microtubule growth within the mitotic spindle and if it is required to stabilise microtubules at specific sites within the spindle.