PhD Study : Role of novel cardiac biomarkers in cellular senescence

Summary

Coronary Artery Disease (CAD) is the largest contributor to Cardiovascular Disease, and accounts for over a quarter of all deaths in Northern Ireland. Currently there is no definitive way to predict cardiac events. There is a crucial need therefore to develop better tests to predict those at risk of cardiovascular events for better disease management and ultimately to improve patient outcomes. In addition, little is known about molecular pathways impacted by many newly discovered cardiac biomarkers at NICSM, C-TRIC (These proteins are in the process of patent filing).

Recently, senescence was identified as the primary contributor to many age-associated diseases including CAD. We have undertaken a feasibility study on senescent proteins taking a multiplex proteomic approach in a prospective cohort of patients with CAD. Machine learning techniques were applied to the senescence related proteins identified, to yield predictive combinations that were able to accurately identify the CAD patients.

A combination of just 3 senescence proteins was able to distinguish very high risk CAD patients from low risk with more than 97% accuracy. We cannot disclose names of these proteins due to intellectual property concerns, however, we want to urgently investigate their contribution to disease progression in cellular models. Not much is known about molecular pathways impacted by these senescence specific proteins.

The proposed project will manipulate these senescence proteins in different models of senescence. We will perform RNA seq analysis on senescent cells with or without these biomarkers to uncover disease specific pathways impacted. We will use our newly established Cardiac Fibroblast senescence model system. Cardiac fibroblast cells can be made senescent just by adding DNA damaging agents such as etoposide and doxorubicin. We will also overexpress these biomarkers using standard techniques (such as pLenti-6 based overexpression) and investigate their contribution to the senescence program. We believe this could lead to discovery of innovative treatment options for CAD.

The proposed 3-year project will be based at soon to be established CardioRISC centre within the THRIVE project of the city deal. The project will also involve active collaboration with Professor Peace, Consultant Cardiologist at Altnagelvin Hospital. One of the central focus of THRIVE project is disease prevention and postponing or delaying the age of chronic disease onset.

This project targets senescence, one of the main drivers of age related chronic diseases. The proteins to be investigated are part of 5 IDFs submitted for patent filings.

AccessNI clearance required

Please note, the successful candidate will be required to obtain AccessNI clearance prior to registration due to the nature of the project.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal
• Clearly defined research proposal detailing background, research questions, aims and methodology

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Experience using research methods or other approaches relevant to the subject domain
• Sound understanding of subject area as evidenced by a comprehensive research proposal
• Work experience relevant to the proposed project
• Publications record appropriate to career stage
• Experience of presentation of research findings
• A comprehensive and articulate personal statement
• Relevant professional qualification and/or a Degree in a Health or Health related area

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living