The role of calcium overload in myocardial ischemia / reperfusion injury

Summary

This project aims to identify the biochemical targets of calcium overload responsible for ischemia / reperfusion injury in the heart.

Supervisor(s)

Dr Stuart Cordwell

Research Location

School of Molecular Bioscience

Program Type

Masters/PHD

Synopsis

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. 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.

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Keywords

Ischemia / Reperfusion Injury, Myocardium, cardiovascular disease, Proteomics, Phosphorylation, oxidative stress, Calcium, Chromatography, mass spectrometry, Cardiovascular & respiratory diseases, Cell biology, Heart & circulation

Opportunity ID

The opportunity ID for this research opportunity is: 63

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