Exploring the links between cardiac arrhythmias and mitochondrial dysfunction

Mitochondria play a central role in the maintenance of homeostasis in cardiomyocytes by regulating several key processes, (e.g. cellular energetics, metabolism, and cell death). Mitochondrial dysfunction is characterised by reduced ATP synthesis and increased ROS production that can lead to cellular and ionic malfunction of the heart, including increased risk of arrhythmic events. Mechanistically, mitochondrial dysfunction is closely related to the pathogenesis of arrhythmias through regulation of the activities of sarcolemmal and mitochondrial cation channels for Na+, Ca2+, and K+, thus leading to cardiac electrical remodelling. Despite extensive research and novel treatments, conditions associated with deranged cardiac metabolism and mitochondrial functions (e.g. heart failure), are still associated with a substantial risk of arrhythmic events. Improving our understanding of the characteristics of the arrhythmic risk is likely to identify novel and more effective therapies.

Abnormal ion channel function and subsequent ventricular dysfunction has been described in hereditary cardiac diseases, such as Long QT and Brugada syndromes. The cardiac voltage-gated Na+ channel Nav1.5/Scn5a is the major isoform expressed in the mammalian myocardium and plays a fundamental role in cardiac excitability/conduction, as it initiates the action potential. We will use gain- and loss-of-function approaches in cardiomyocytes to determine i) how Na+ channelopathy affects mitochondrial functions, and ii) whether activation of the homeostatic mitochondrial stress response (UPRmt) can improve the adverse effects observed during Na+ channel dysfunction.

This is an exciting, fully-funded, collaborative project between the University of Surrey (UoS) (Dr Ioannis Smyrnias and Prof Kamalan Jeevaratnam) and the National University of Singapore (NUS; https://medicine.nus.edu.sg/trp/cardiovascular-disease/) (Dr Chester Lee Drum). The student will be registered at UoS, where they will spend a minimum of 2 years, before they visit NUS for approximately 1 year to complete the project.

You will need to meet the minimum entry requirements for our Veterinary Medicine and Science PhD programme.

Open to candidates who pay UK/home rate fees. See UKCISA for further information.

Applicants should have a first-class or upper second-class honours or equivalents in Biochemistry, Biomedical Sciences, Biomedical Engineering, Biological Sciences, Physiology, or similar subjects.

Practical experience of cell biology, platelet biology or cell signalling is desirable but not essential.

It is ‘essential’ for the successful candidate to have:

• BSc degree, or equivalent, in a relevant discipline
• Previous experience with aseptic cell culture, fundamental molecular biology/biochemistry and imaging techniques (e.g. real-time PCR, western blotting, immunofluorescence)
• Excellent communication and organisational skills
• Ability to work independently and as part of a team.