Project Description: Chromosomal instability (CIN) and aneuploidy are hallmarks of cancer caused by chromosome aberrations acquired as cells divide (in mitosis). They are features of most solid tumours and ~60% of hematopoietic cancers and established markers of drug resistance and clinical outcome. Evasion of cell death (apoptosis) is a key mechanism associated with CIN in cancer. Our work has found a novel and important role for the cell death protease and tumour suppressor protein, caspase-2, in limiting aneuploidy and preventing CIN. Reduced CASP2 expression is often associated with chromosome deletion or transcript levels in many tumours and correlates with CIN, intra-tumour heterogeneity, tumour relapse and drug resistance. This project will investigate the mechanisms that regulate caspase-2 activation and function in order to establish how it helps prevent aneuploidy and tumourigenesis. As part of this we are examining the protein modifications in caspase-2 (e.g. phosphorylation), critical for regulating its activation. This project involves using mouse models to establish whether different caspase-2 protein modifications affect its tumour suppression function. These studies have the potential to identify novel biomarkers and targets for the prognosis and treatment of different cancers.
Pre-requisite skills: Basic laboratory skills are a must. An understanding of Cell and Molecular Biology is important with skills in microscopy, cell culture and protein biology. Some experience with mouse handling is desirable.
Supervisors: Dr Loretta Dorstyn and Professor Sharad Kumar
Supervisor contact email: loretta.dorstyn@unisa.edu.au
