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MRC DiMeN Doctoral Training Partnership: Towards greater understanding of Atrial Fibrillation: Proteomics and genomics of a common global cardiac rhythm disorder


Project Description

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, leading to a major public health impact, especially due to increased risk of stroke and hospitalizations.

Cardiac remodelling arising from altered protein expression results in electrical, contractile and structural changes leading to an altered heart rhythm in patients which can be progressive in a large number of patients. The severity of AF ranges from paroxysmal AF which is self-terminating (usually within 48 h) to longstanding persistent AF (where the arrhythmia has lasted for 1 year or more in which a rhythm control strategy is used normally via catheter ablation) through to permanent AF (when the presence of the arrhythmia is constant).

In this project we aim to understand the differences in the multiple sub-types of AF as a means of understanding individual manifestations as well as progression of disease and the ageing process. This project will use human patient samples, and compare protein and genetic differences between paroxysmal, persistent and permanent AF. Since AF is known to progress in severity over the ageing process we will further use animal models of AF to monitor functional and structural changes over time. Taken together we aim to identify changes at the molecular, cellular and physiological levels that lead to an increased risk of AF. We will use high-end proteomics and genomics to identify pathways and biomarkers involved in disease. Once differentially expressed proteins have been identified we will investigate these further using in vitro 2D and 3D cardiac systems established within our group.

Catheter ablation is a frequently used treatment method for the restoration of normal heart rhythm in AF patients. This project will further compare samples pre- and post-ablation to see how rhythm management alters the protein profile in patients.

The research outlined will be carried out at the new Liverpool Centre for Cardiovascular Science, linking the Liverpool Heart and Chest Hospital (LHCH, where the primary supervisor is a Consultant Cardiologist) and the University of Liverpool (UoL), 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, genomic and trained how to statistically analyse data generated using state of the art software. You will further be trained in cell culture techniques to investigate proteins of interest as well as analytical techniques to look at cardiac cell health by assessing key phenotypes such as viability, morphology, beat rates and assessment of known biomarkers of cell damage. We will confirm protein changes by Western blot level using molecular techniques and morphological changes by immunofluorescence.

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 patient lives.

Websites
1. Prof Gregory Y.H. Lip http://www.liverpool.ac.uk/lccs and https://www.birmingham.ac.uk/staff/profiles/cardiovascular-sciences/Lip-Gregory.aspx
2. Dr 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 benefitted from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs
Includes:
Stipend at national UKRI standard rate
Tuition fees
Research training and support grant (RTSG)
Travel allowance
Studentships commence: 1st October 2019.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website
Good luck.

References

Khan AA, Lip GYH. The prothrombotic state in atrial fibrillation:
pathophysiological and management implications. Cardiovasc Res. 2018 Nov 2. doi: 10.1093/cvr/cvy272.

Thomas MR, Lip GY. Novel Risk Markers and Risk Assessments for Cardiovascular Disease. Circ Res. 2017 Jan 6;120(1):133-149.

2014 Research Excellence Framework (REF) Impact Case Study: http://impact.ref.ac.uk/CaseStudies/CaseStudy.aspx?Id=38790

How good is research at University of Liverpool in Clinical Medicine?
(joint submission with Liverpool School of Tropical Medicine)

FTE Category A staff submitted: 143.50

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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