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)

Professor Stuart Cordwell

Research Location

School of Life and Environmental Sciences

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.

Additional Information

HDR Inherent Requirements

In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:

- Confidential disclosure and registration of a disability that may hinder your performance in your degree;
- Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
- Ability to perform independently and/or with minimal supervision;
- Ability to undertake certain physical tasks (e.g. heavy lifting);
- Ability to undertake observatory, sensory and communication tasks;
- Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);
- Ability to work in confined spaces or at heights;
- Ability to operate heavy machinery (e.g. farming equipment);
- Hold or acquire an Australian driver’s licence;
- Hold a current scuba diving license;
- Hold a current Working with Children Check;
- Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)

You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.

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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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