UPDATE April 2013: The Position has now been filled, thank you to all those who applied.
I am currently looking for PhD students to take on either of the following two exciting projects in the lab.
For further information please contact either:
Dr Andrew Burgess via email: a.burgess ‘at’ garvan.org.au or
Dr Alessandra Bray at the Institute on +61 2 9295 8251 or email: a.bray”at”garvan.org.au.
During mitotic exit certain CDK1 substrates need to remain phosphorylated while others must be dephosphorylated to ensure the highly ordered events of mitotic exit occur in the correct sequence. However, currently very little is known about how this order of dephosphorylation is achieved in mammalian cells. This project aims to identify the order of substrate dephosphorylation and the phosphatase responsible. The project will utilize quantitative live and fixed microscopy, advanced biochemistry and Mass Spectrometry techniques. The outcomes will dramatically advance our understanding of this fundamental stage of cell division, and may identify novel targets for future chemotherapies.
Project 2: Preventing Mitotic Exit to Kill Cancer.
Many classical and new-line chemotherapeutics target mitosis as a means of selectively killing cancer cells. Unfortunately, many cancer cells are resistant to these drugs. Furthermore, it is very difficult to currently predict which cancers will be sensitive or resistant. This project aims to identify a common signature of proteins that promote and inhibit mitosis and determine if these can be used to predict response, and if subsequent targeting of these proteins improves current chemotherapies. This project will utilize multiple cancer cell line models, immunohistochemistry, and advanced live-cell imaging. The outcomes will hopefully provide a critical predictive tool and help further our understanding of why cancer cells are sensitive or resistant to mitotic poisons.
About the Lab
The Mitotic Control Group sits within the Cell Cycle group (Prof. Liz Musgrove) of the Garvan’s Cancer Research Program. It is a new exciting team that is focused on targeting novel mitotic checkpoint pathways to selectively target cancer cells. Recently, we demonstrated that correct mitotic progression was dependent on maintaining a tightly regulated balance between the activities of the phosphatase PP2A, and kinase CDK1 [1,2]. Further, we identified the novel mitotic kinase Greatwall as the master regulator of this balance [3,4]. These results dramatically altered our understanding of mitosis and opened up several new and exciting research pathways. The primary aim of the lab is to further explore and characterise these pathways, to identify new chemotherapeutic targets and improve the sensitivity and selectivity of existing cancer drugs.
1. Burgess A, Vigneron S, Brioudes E, Labbé J-C, Lorca T, et al. (2010) Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance. Proc Natl Acad Sci USA 107: 12564–12569.
2. Lorca T, Bernis C, Vigneron S, Burgess A, Brioudes E, et al. (2010) Constant regulation of both the MPF amplification loop and the Greatwall-PP2A pathway is required for metaphase II arrest and correct entry into the first embryonic cell cycle. J Cell Sci 123: 2281–2291.
3. Gharbi-Ayachi A, Labbé J-C, Burgess A, Vigneron S, Strub J-M, et al. (2010) The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A. Science 330: 1673–1677.
4. Vigneron S, Brioudes E, Burgess A, Labbé J-C, Lorca T, et al. (2009) Greatwall maintains mitosis through regulation of PP2A. EMBO J 28: 2786–2793.