Student research project
Heart failure is a debilitating condition in which the ability of the heart to meet the body's demands for oxygenated blood is compromised. Prognosis is poor, with approximately 50 per cent of patients with heart failure dying within 5 years of diagnosis. Thus, there is a clear need for new therapeutic strategies for the treatment of heart failure.
Cardiac hypertrophy (an increase in heart muscle mass) is a key feature of the pathological cardiac remodelling that occurs following an acute cardiac injury (e.g. myocardial infarction) and in settings of chronic pressure overload (e.g. hypertension), and contributes to the development of heart failure. Investigation of the signalling mechanisms responsible for initiating and sustaining cardiac hypertrophy may lead to the identification of novel therapeutic strategies for the treatment of heart failure.
The aim of this project will be to investigate the role of a protein phosphatase known as B55α-PP2A in the regulation of cardiac hypertrophy. Dr Weeks recently identified B55α-PP2A as an important regulator of HDAC5 downstream of β-adrenergic receptor stimulation in cardiomyocytes (J Am Heart Assoc 2017). It is hypothesised that B55α-PP2A is an important regulator of cardiomyocyte size (via its effects on HDAC5), and that dysregulation of B55α-PP2A in settings of cardiovascular disease plays a causal role in the development of cardiac hypertrophy and/or heart failure.
Related methods, skills or technologies
The project is suitable for an Honours student and will involve pharmacological experiments in primary cardiomyocytes and immortalised cell lines. You would gain expertise in molecular biology techniques, such as cloning, mutagenesis, RT-qPCR, co-immunoprecipitations, SDS-PAGE and Western blotting. The data obtained from this project will complement in vivo studies currently being conducted by the Cardiac Hypertrophy Laboratory.