Role of degradation systems in regulating inflammation in heart failure

The King’s College London British Heart Foundation (BHF) Centre of Research Excellence offers an outstanding environment for cardiovascular research training. It includes a large number of internationally rated investigators whose expertise encompasses a very broad range of cardiac and vascular biomedicine. The unit performed exceedingly well in the recent RAE, being the only institution to be in the top 3 both on average quality score and research power.

We are inviting applications for 3-year interdisciplinary studentships to commence from October 2012 that are each co-supervised by a cardiovascular and a non-cardiovascular PI with distinct complementary expertise. All principal supervisors on the programme have a strong track record of publications, grant income and successful supervision. Applications from non-biomedical graduates with relevant training are particularly welcome.


Project Information

Supervisors: Professor Kinya Otsu and Professor Frederic Geissmann

Heart failure is a leading cause of morbidity and mortality in the UK. Increased levels of circulating proinflammatory cytokines, such as TNF-, IL-6 and IL-1 are associated with disease progression and adverse outcomes in chronic heart failure patients. Although infection with microorganisms is not involved in the development of heart failure in most cases, inflammation has been implicated in the pathogenesis of heart failure. However, the mechanisms responsible for initiating and integrating inflammatory responses within the heart remain poorly defined. .

Mitochondria (evolutionary endosymbionts derived from bacteria) damaged by external hemodynamic stress are degraded by the autophagy/lysosome system in cardiomyocytes. We have previously reported that autophagy is an adaptive mechanism to protect the heart from hemodynamic stress. More recently, we showed that mitochondrial DNA that escapes from autophagy cell-autonomously leads to Toll-like receptor (TLR) 9-mediated inflammatory responses in cardiomyocytes and is capable of inducing myocarditis, and dilated cardiomyopathy.

The level of the inflammatory cytokines is regulated by both their synthesis and degradation. The importance of their degradation in the genesis of heart failure remains to be elucidated. The RNase regnase-1 and tristetraproline (TTP) serve a critical role in preventing inflammation by controlling the stability of mRNAs that encode cytokines.

This project will investigate the role of RNA degradation in isoproterenol-mediated cardiac hypertrophy and heart failure using isoproterenol infusion.

This project aims:

- To elucidate the role of RNA degradation in inflammation and cardiac dysfunction in failing hearts.
- To examine whether the regulation of RNA degradation may be a novel therapeutic approach to treat patients with heart failure.


NOTE: THIS IS 1 OF 4 AVAILABLE PROJECTS. FOR INFORMATION ON THE OTHER 3 PROJECTS SEE THE ''ALL PHDS IN THIS DEPT" LINK ON THE RIGHT-HAND SIDE. STUDENTS CAN CHOOSE UP TO 2 PROJECTS TO APPLY FOR.


Candidates must possess, or be expected to achieve, a 1st or good upper 2nd class degree in a relevant subject and must meet BHF residency requirements. Current 1st year BHF stipend rates for London are £21,629 pa.

For further information please visit our website via the link below

Application procedure:

- Apply online https://myapplication.kcl.ac.uk/ for the School of Medicine, Cardiovascular Research Division MPhil/PhD (Full-time) programme and quote reference 03/12PHD on the ‘Research Proposal’ page

- There is no need to write a research proposal. Instead please state which project(s) you wish to apply for in this section of the form.

- Please include a personal statement outlining your suitability for the programme and why you are interested in pursuing a PhD in the subject area.


Closing date: Wednesday 11th April 2012

Enquiries:
Should you have any enquiries please contact Elizabeth Halton, Assistant Divisional Manager, on [Email Address Removed] or (020) 7848 0263.


Please ensure that you quote 03/12PHD on your application and state clearly which project(s) you wish to apply for. Details on the other available projects can be found on our web site or by clicking on the 'All PhDs in this Dept' link on the right.