Inflammatory pathways in obesity lead to mitochondrial dysfunction in the heart

Globally, the number of individuals considered obese has reached pandemic proportions. Obesity triggers a cascade of pathophysiological signalling pathways and is one of the co-morbidities associated with the development of type 2 diabetes. Cardiovascular complications are one of the leading causes of death in patients with diabetes.

Cardiac mitochondrial dysfunction has been established both in patients who are obese and with type 2 diabetes, but the molecular mechanisms involved are complex and remain poorly understood. One hallmark of obesity is chronic inflammation and a link between the mitochondrial fission protein mitofusin-2 and inflammatory signalling pathways has been indicated in skeletal muscle. However, the molecular and cellular mechanisms are yet to be defined and have not been examined within the heart.

This project will investigate the impact of specific inflammatory triggers upon mitochondrial function and morphology with a particular emphasis upon fission and fusion, since these processes impact not only upon mitochondria morphology but also upon mitochondrial bioenergetics. The project will also investigate whether pharmacological interventions disrupting inflammation driven signalling cascades have beneficial effects upon mitochondrial structure and function and thus will represent a novel cardioprotective strategy.

The successful candidate will be trained in a wide range of techniques including cell culture, 3D electron microscopy, analysis of the mitochondrial energy phenotype, molecular biology techniques and enzymatic assays. There will also be opportunities to learn in-vivo techniques such as echocardiography.

Candidates are expected to hold a minimum of an upper second class (or equivalent) undergraduate degree in a bioscience related discipline.

This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/ sponsorship and is due to commence from January 2017 onwards.

Any enquiries relating to the project and/or suitability should be directed to Dr Kitmitto ([Email Address Removed]). Applications are invited on an on-going basis but early expression of interest is encouraged.