The prevalence of heart failure (HF) in the UK is increasing with close to 1 million individuals with HF in the UK alone due to an increase in the ageing population. Prognosis of HF remains poor, however, advances in the management of HF are limited because the pathophysiological mechanisms are incompletely understood. Using metabolomics analysis we have shown significant increases in the metabolite ketoglutarate in the serum of HF patients.
Ketoglutarate is a citric acid cycle intermediate and in addition to its role in energy production, ketoglutarate can bind to a G-protein coupled receptor (GPR99) and may produce biological actions through its activation. Our preliminary data shows that cardiomyocytes express the GPR99 receptor and when treated with ketoglutarate display an increased level of VEGFR-1 and PGF, two key regulators of cardiac hypertophy and angiogenesis. Based on successful preliminary data, this project will explore the entirely novel idea that ketoglutarate is pivotal in modulating hypertrophy (enlargement of the heart), a key process in the progression of HF.
The main aims of the study will be to:
- Investigate the effects of GPR99 over-expression in cardiomyocyte hypertrophy.
- Investigate the effects of GPR99 gene ablation in mice.
Overall, this project will determine the role of ketoglutarate and its receptor in the pathophysiology of HF. It will also provide a unique combination of training in molecular biology and in vivo animal physiology for the successful applicant.
The project will be conducted within the Cardiovascular Research Group, an internationally recognised group ranked within the top four in the 2008 UK RAE. Extensive training in molecular cellular biology and in vivo animal physiology will be provided. Completion of this project would equip the candidate for progression into academic biomedical research as well as the biomedical industry.
Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in biochemistry, physiology, biological/medical sciences, pharmacology or a related area. A Masters degree in a similar area would be an advantage.
This 3-year project is open to UK/EU and non-EU nationals but no funding is provided. Applicants must therefore be able to provide evidence of their ability to provide self-arranged funding. Annual tuition fees for this project are currently:
*UK/EU nationals: £6, 300
Non-EU nationals: £17, 000
Please direct applications in the following format to the project lead, Dr Delvac Oceandy (delvac.oceandy@manchester.ac.uk):
• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date
• Evidence of funding.
Any enquiries relating to the project and/or suitability should be directed to Dr Oceandy at the address above.
http://www.medicine.manchester.ac.uk/cardiovascular/
http://www.medicine.manchester.ac.uk/staff/delvacoceandy
Funding Notes:
*UK/EU nationals should note that the fee is subject to an annual increase of approxmately 2.5%
Please quote 10 Academic Resources Daily in your application to this opportunity!
