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Diagnostic epigenetic markers for myocardial injury risk stratification

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  • Full or part time
    Dr S Pennings
    Dr Douglas VERNIMMEN
    Dr Fiona Strachan
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

The newly established four-year Medical Sciences & Translational Research PhD with integrated studies in Engagement for Impact Programme will combine medical science and translational research projects with integrated and credited teaching in science communication, public engagement, patient involvement, data design and informatics, via established MSc courses and/or new Engagement for Impact courses. Our vision is to teach a generation of researchers equipped to address and solve real-world problems through excellent science and who have the engagement and impact skills we believe will give them an edge in their future careers.
https://www.ed.ac.uk/inflammation-research/postgraduate-training/phd-programme

This potential PhD project, selectable by successful applicants to this Programme, is supervised by Dr Sari Pennings (https://www.ed.ac.uk/profile/sari-pennings) at the Centre for Cardiovascular Science, with co-supervisors Dr Douglas Vernimmen and Dr Fiona Strachan.

Project Summary:
Lower cardiac troponin (a heart muscle marker) diagnostic thresholds for myocardial infarction have been linked to improved patient outcomes. Increasingly sensitive assays can exclude a myocardial infarction diagnosis below the low risk threshold1. For patients at intermediate risk below the diagnostic thresholds, the damage and treatment pathways remain uncertain. High-sensitivity assays allow for intermediate risk stratification in patients with suspected acute coronary syndrome, with refinement by additional clinical characteristics. New blood biomarkers are needed to further improve diagnostic discrimination between myocardial injury types. Building on this expertise, we aim to develop cardiac epigenetic assays for clinical translation.
Myocardial injury or cardiometabolic risk is associated with a detection of higher levels of circulating cell-free DNA compared to healthy individuals, a potential diagnostic biomarker that can report specifically on cardiomyocyte damage2. Circulating chromatin fragments originate from apoptosis and therefore directly evidence tissue injury3. This PhD study aims to develop blood assays for epigenetic biomarkers4,5, to test their potential for stratifying intermediate risks and understanding early vs. reversible myocardial injury. Furthermore the study will investigate how epigenetic mapping of circulating cell-free DNA and chromatin markers including antibody based immunoassays can report on epigenetic profiles of the original cells’ disease state6.

References:
1. Anand A, Mills NL. Cardiovasc Res. 2019 Dec 1;115(14):e158-e160.
2. Zemmour H, et al Nat Commun. 2018 Apr 24;9(1):1443.
3. Aguilar-Sanchez C, … Pennings S. Stem Cells Int. 2018 Jun 24;2018:1247857.
4. van de Lagemaat LN, … Vernimmen D. Epigenetics Chromatin. 2018 Oct 6;11(1):59.
5. Paris J, et al. Cell Stem Cell. 2019 Jul 3;25(1):137-148.e6.
6. Beaujean N, … Pennings S. Methods Mol Biol. 2018;1708:59-80.
7. Shah ASV, et al. BMJ. 2017 Nov 7;359:j4788.


Engagement for Impact:
The PhD supervisory team’s extensive complementary expertise in public engagement with research includes novel activity design, media communication including cinematography for public impact, engagement with patient support groups, and patient engagement panels contributing to clinical trial design. Our Centres are leading on clinical and biomedical public engagement and offer an environment, in which PhD student-led engagement can thrive. The student will interact with audiences relevant to this research: patients and families support groups, funders and charities, the general public, and health care policy makers.
As PhD student you will develop a programme of public engagement for impact, exploring different ways of engaging. Our clinical studies offer an opportunity to evaluate impact of patient engagement on trial design and also trust7, by analysing data from this exemplar of ‘research co-production’ towards clinical research outcomes. Our research addresses important issues in health equity, such as gender- differences in clinical research, and social and healthcare provision in the community, where chronic heart failure affects older and economically disadvantaged sections of society. These and the growing health care burden of cardiovascular disease on health care systems require further analysis and inquiry grounded in theoretical frameworks of ‘knowledge to action’ and ‘learning health systems’.
The PhD student will develop public engagement activities with research, with patient groups and other interest groups. Focusing on what occurs ’When Heart Cells Die’, audiences will learn how patients’ blood samples have contributed diagnostic markers improving long term treatments, highlighting the importance of ongoing research to find DNA biomarkers that can detect heart injury earlier and understand how this differs from healthy heart exertion.

Funding Notes

This is one of the potential projects in the University of Edinburgh College of Medicine and Veterinary Medicine’s new 4 year Medical Sciences & Translational Research PhD with integrated studies in Engagement for Impact Programme. Successful applicants will select their preferred PhD projects from the available options in discussion with proposed supervisors. Three studentships are available in the programme, providing full tuition fees (EU/UK rate only), stipend of at least £15,000 per year, £450 annual travel and conference allowance, dedicated engagement support grant of £1,500, and £5,000 annually towards research consumable costs.
Apply before 26th January 2020 at https://www.ed.ac.uk/inflammation-research/postgraduate-training/phd-programme




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