Cardiac Proteomics Laboratory - Honours projects available in 2009
An Honours project undertaken in this lab would be administered by the Discipline of Pathology.
This group uses the tools of proteomics to investigate markers of heart disease and the post-translational modification of proteins / peptides during ischemic heart disease. Specific techniques include liquid chromatography, electrophoresis, mass spectrometry.
- Recent interesting publications:
- White, M.Y., Gundry, R.L. and Cordwell, S.J. (2006) When does a fingerprint constitute a diagnostic? The Lancet 368: 971-973.
- White, M.Y., Tchen, A.S., McCarron, H.C.K., Hambly, B.D., Jeremy, R.W. and Cordwell, S.J. (2006) Proteomics of ischemia and reperfusion injuries in rabbit myocardium with and without intervention by an oxygen free radical scavenger. Proteomics 6: 6221-6233.
- White, M.Y., Hambly, B.D., Jeremy, R.W. and Cordwell, S.J. (2006) Ischemia-specific phosphorylation and myofilament translocation of Hsp27 precedes alpha B-crystallin and occurs independently of reactive oxygen species in rabbit myocardium. Journal of Molecular and Cellular Cardiology 40: 761-774.
- Peptide biomarkers of myocardial ischemia
Supervisor + contact details:
- Dr Stuart Cordwell
- Associate Professor Brett Hambly
- Dr Melanie White
Cardiovascular disease (CVD) results in approximately 7 million deaths per annum world-wide and is the most significant cause of death in Australians. Many of these result from sequelae following myocardial ischemia / reperfusion (I/R) injury. Reduction or cessation of blood flow (ischemia) generally results from the formation of atherosclerotic lesions in the coronary arteries. Reintroduction of blood-flow (reperfusion) by thrombolysis or primary percutaneous coronary artery intervention remains the best strategy for resolving ischemia and preventing cell death and permanent cardiac dysfunction (infarction). Morbidity and mortality from acute myocardial infarction (AMI) remain significant. The endogenous or "native" peptidome is the full complement of natural, low molecular mass (<10kDa) peptides, as well as those created by the proteolysis of larger proteins, contained within a cell, tissue or body fluid. Pathology is often underpinned by protein damage, particularly following protease activation. The peptidome is therefore a rich source of putative disease biomarkers. This project will utilize chromatography coupled with mass spectrometry to identify peptide biomarkers of I/R injury in animal models and thus act as a model for developing new and more effective strategy for the rapid diagnosis of myocardial ischemia.
- The role of calcium overload in myocardial I/R injury
Supervisor + contact details:
- Dr Stuart Cordwell
- Associate Professor Brett Hambly
At the cardiomyocyte level, I/R injury is characterized by Ca2+ overload and the generation of ROS. Both are highly reactive molecules and are able to interact with almost any biological substrate. Lipids and proteins are possible targets, with potentially wide-reaching implications - lipid damage will affect the integrity and permeability of cell membranes, while protein damage may change the functionality of regulatory enzymes or contractile mediators. We have previously investigated the role of ROS on protein post-translational modification in I/R injury. In this project, proteomics will be used to investigate the effects of Ca2+ overload on proteins within myocardial tissue during I/R. The project will involve animal studies (Langendorf perfusion surgery), as well as biochemical assays including two-dimensional electrophoresis and mass spectrometry. These studies will identify proteins damaged during I/R and potentially lead to clinical therapies.
