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Centrosome biology

Our group wants to shed light on the basic principles of cell division and understand how abnormal cell divisions contribute to pathologies.

For organisms to survive, their cells need to be continuously replenished through cell divisions. It is crucial that cells pass on a complete set of genes every time they divide. This is achieved by the faithful replication of our chromosomes, followed by their equal segregation between daughter cells. Chromosomes are anchored to and distributed by the mitotic spindle, a symmetric bipolar structure, composed of protein fibres called microtubules. The poles of the spindle are formed by centrosomes, specialised organelles that produce and organise microtubules.

The centrosome is 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.