Targeting novel regulators of exercise induced heart growth to treat heart failure and complications

Student research project

Supervisor(s): Professor Julie McMullen

Project summary

Heart failure is a major clinical problem affecting 1–2 per cent of Australians. The number of people diagnosed with heart failure is on the rise, due to an ageing population and increased rates of obesity and diabetes, posing a significant healthcare burden. Thus, strategies to protect the heart against insults such as high blood pressure, heart failure and heart attack are becoming even more critical. The Cardiac Hypertrophy laboratory is focused on identifying genes/proteins that mimic the protective effects of exercise. Growth of the heart (also termed cardiac hypertrophy) can be induced by physiological stimuli (e.g. postnatal development, chronic exercise training) or pathological stimuli (e.g. high blood pressure). Physiological hypertrophy ('good' heart growth) is characterised by a normal organisation of cardiac structure and normal or enhanced cardiac function. Whereas, pathological hypertrophy ('bad' heart growth) is associated with cardiac dysfunction, and increased morbidity and mortality.

In an effort to treat patients with heart failure, the majority of investigators have focused on blocking 'bad' genes and signalling pathways in the heart, which largely delays heart failure. By contrast, my laboratory are examining the possibility of activating 'good' genes and signalling pathways that may normally be activated during the induction of physiological hypertrophy (e.g. in the 'athlete’s heart'). My group previously reported that the insulin-like growth factor 1 (IGF-1)-phosphoinositide 3-kinase (PI3K) pathway plays a critical role for the induction of exercise induced heart growth. Thus, activation of PI3K, or novel regulators of this pathway, represents a promising new strategy to treat heart failure.

We have a number of projects that target the IGF1-PI3K pathway by using novel drugs or gene therapy approaches (adeno-associated viruses or microRNA-based therapies). Projects utilise genetic mouse models in combination with a number of molecular biology and biochemical techniques.

Related methods, skills or technologies

The project is suitable for an Honours, Masters or PhD student and will involve applying various skills and techniques, including:

• cell culture
• molecular biology
• echocardiography/ECG
• Langendorff studies
• adult myocyte isolation
• cloning.

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