Research

Centrosomal signalling in cell cycle regulation

The centrosome is a multifunctional organelle involved in organising the microtubule network. Another less well understood role of the centrosome is its function as a cell cycle regulator. The centrosome mediates cell cycle progression by acting as a scaffold by which proteins from various signalling networks interact to influence the activity of key cell cycle regulators, such as Cdk1-Cyclin B. The loss of centrosomal components can result in the deregulation of cell cycle controls. For example, deleterious mutations on the centrosomal protein PCNT causes cells to loose its ability to arrest its cell cycle in the presence of DNA damage. This is caused by the failure of the centrosome in recruiting the cell cycle regulator Chk1 to the centrosome.

Our lab is interested in elucidating how signals are integrated at the centrosome to regulate cell cycle transitions.

Another area of interest in the lab is the phenomenon of centrosomal defects in cancer. Centrosomal defects are common in high grade cancer and have been shown to trigger tumorigenesis in mice. It is likely that centrosomal defects observed in cancers would result in the deregulation of cell cycle controls.

Developing computational tools for single cell analysis

Quantitative single-cell analysis has revolutionised our approach in studying the molecular events that lead to cell fate decisions. A common challenge when performing single-cell analysis is the limited tools available to accurately track, segment and measure signalling events within the cell. Our lab is actively developing methods to overcome this limitation by combining cutting edge machine learning approaches with established cell biological techniques to allow the accurate segmentation and tracking of cellular events within the cell.

In addition, we are also actively developing novel fluorescent biosensors to enable the study of various signalling networks within the cell.

Details on the computational approaches developed in our lab can be found here: https://github.com/chan-labsite