Cell Cycle Unit, Children's Medical Resarch Institute, Westmead

Lab head: Dr Megan Chircop
Location: Children's Medical Research Institute


Phospho-regulation of centrosome proteins in cancer cells

Primary supervisor: Rose Boutros

Centrosomes are the primary microtubule organising centres of cells, forming the interphase microtubules and the bipolar spindle during mitosis. Abnormal centrosomes or number of centrosomes develop into dysfunctional mitotic spindles with consequent errors in chromosome separation. This results in aneuploid cells, which can drive tumourigenesis and are a common characteristic of cancer. Thus, it is not surprising that centrosome defects have been shown to contribute to the transformation of a normal epithelial cell into a malignant cell. Phosphorylation is a reversible post-translational modification that regulates most cellular processes, including the duplication of the centrosome during cell division. A recent centrosome phosphoproteome study in yeast (Keck et al. Science 332:1557, 2011) identified nearly 300 phosphorylation sites in 14 of the 18 yeast centrosome proteins, many of which are highly conserved throughout evolution. This study will therefore investigate the role of phosphorylation of one of these key centrosome proteins in mammalian cells. The conserved phosphosites identified by Keck et al. will be mutated in the human gene by site-directed mutagenesis into phospho-mimetic and phospho-deficient forms. These will be expressed as GFP-tagged fusion proteins in human cancer cell lines in addition to the wild-type protein and their effects on centrosomal function and protein-protein interactions will be examined.

Discipline: Pathology
Co-supervisors: Megan Chircop
Keywords: Proteomics, Cell biology, Cancer