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MRC DiMeN Doctoral Training Partnership: Is your heart ageing faster than the rest of you? Is inflammation-related cardiac disease making your heart age faster than it should?


MRC DiMeN Doctoral Training Partnership

Liverpool United Kingdom Bioinformatics Cardiology Cell Biology Data Analysis Molecular Biology Pharmacology Toxicology

About the Project

Background

Heart disease is the leading cause of global morbidity and mortality with numbers continually increasing as the global population ages. Atrial fibrillation (AF) is the most common heart rhythm disorder in the world effecting between 1-2% of the general global population and its prevalence roughly doubles with each advancing decade of age, from 0.5% at age 50–59 years to 10-15% at age 80–89 years. The presence of AF is associated with serious complications including heart failure, dementia and stroke. Recent findings suggest that inflammatory signalling contributes to the development of age-related cardiovascular diseases including AF and that genes implicated in cellular senescence are regulated by inflammation further aging the heart. 

Aim

In this project we aim to understand the contribution inflammation in AF by comparison of atrial tissue from patients with AF and those undergoing mitral valve surgeries as a ‘control group’ without AF. Further it is predicated that approximately 30% of patients in the ‘control group’ will develop post-operative incident AF following surgery. Differences between patients that do develop post-operative AF, and those that do not, will be studied. We further aim to investigate the mechanistic changes in patients using patient derived atrial cardiomyocytes generated using induced pluripotent stem cells (iPSC) reprograming technology.

Training

The research outlined will be carried out at the University of Liverpool (UoL) in the Liverpool Centre for Cardiovascular Science, linking with the Liverpool Heart and Chest Hospital, which houses state-of-the art equipment and laboratories. This is a multi-disciplinary project in which you will be trained how to carry out global proteomics and trained how to statistically analyse data generated using state of the art software. Identified differentially expressed proteins will be analysed using siRNA technology in established 3D cell-based models (primary supervisor) to assess their functional changes by electrophysiology and morphological changes by immunofluorescence. You will learn how to reprogram cells to form atrial cardiomyocytes and gain mechanistic insight into a devastating global condition. Potentially identified biomarkers will ascertain if an early detection panel of AF can be determined. 

Impact

Your research will give mechanistic and translational insights into cardiovascular physiology and pathophysiology, and ascertain how this common global disease manifests and progresses in patients.  This could provide greater diagnostic and prognostic potentials in an effort to improve care of patients with AF.

For more information:

Primary Supervisor: Gregory Lip https://www.liverpool.ac.uk/health-and-life-sciences/staff/gregory-lip/

Secondary Supervisor: Parveen Sharma https://www.liverpool.ac.uk/translational-medicine/staff/parveen-sharma/

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

https://bit.ly/3lQXR8A 


Funding Notes

Studentships are funded by the Medical Research Council (MRC) for 3.5yrs. Funding will cover UK tuition fees and stipend only. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. Please read additional guidance here: View Website
Studentships commence: 1st October 2021
Good luck!

References

1. Bentley, R., Logantha, S. J. R. J., Sharma, P., Rainbow, R. R., & Lip, G. Y. H. (n.d.). Pathophysiological insights into atrial fibrillation: revisiting electrophysiological substrate, anatomical substrate, and possible insights from proteomics. Cardiovascular Research. doi:10.1093/cvr/cvaa276
2. Luigi Ferrucci & Elisa Fabbri (2018) Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty Nature Reviews Cardiology volume 15, pages505–522

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