Centrosome biology

The work in our laboratory focuses on the centrosome, an organelle best known for its role as a major microtubule organising centre.

Emerging evidence, however, suggests that the centrosome also acts as a communication hub that spatially concentrates diverse signalling pathways. While centrosome number and function are strictly regulated within healthy cells, tumours display a multitude of centrosome abnormalities. How such anomalies contribute to tumourigenesis is an important and as yet unresolved question.

In most normal cells the centrosome is composed of a pair of cylindrical structures, the centrioles, which are embedded in an electron-dense amorphous matrix, the pericentriolar material. The latter provides the site for microtubule nucleation and therefore strongly influences microtubule numbers and organisation throughout the cell cycle. Proteomic studies of whole human centrosomes suggest that the organelle contains up to 300 proteins, many with unknown function.

Tumours exhibit a wide variety of centrosome abnormalities that range from numerical and structural, to functional and positional aberrations, but the cause of these is not known. The long-term objective of our group is to provide insight into the molecular pathways that give rise to abnormal centrosome number and function in tumours. Moreover, we will investigate whether abnormal centrosomes constitute valid clinical targets in cancers. To be able to address these questions, we must first obtain better understanding of the processes that underlie normal centrosome function.