Supervisor View 2

My WorkCentrosome abnormalities and amplification are common characteristics of tumour cells. Aneuploidy and chromosomal instability are highly correlated with the appearance of multiple centrosomes. Supernumerary centrosomes can cause mitotic abnormalities, such as the formation of multipolar spindles, potentially giving rise to abnormal chromosome segregation. Normally, centrosome amplification is tightly regulated during the cell cycle. Previous work from our group has demonstrated that DNA damage leads to centrosome amplification. How this happens in tumourigenesis is not well understood. Centrosome defects are also seen in patients with primary microcephaly. We are exploring how mutations in microcephaly genes disrupt the normal controls on centrosome duplication.

Centrosomes also provide the structural basis for primary cilia- small, antenna-like structures that are found on the surface on most cell types. Primary cilia direct cellular responses to chemical and mechanical signals. Defects in ciliation cause a number of developmental disorders that particularly affect organs that respond to fluid flows, including the kidney, eye, liver, brain and skeleton, collectively termed the ciliopathies. Mechanisms that link centrosome mutations to the ciliopathies remain to be explored in detail, as do potential links between ciliopathies and microcephaly.