PhD Study : Metformin as a Potential Therapeutic for Glaucoma

Summary

Metformin, a commonly used drug for type II diabetes (T2DM), is protective against glaucoma development in epidemiological studies. Metformin is a synthetic biguanide and a caloric-restriction mimetic drug. This class of drug can have geroprotective effects delaying or reducing the risk of age-associated systemic diseases. Metformin reduces the risk of primary open angle glaucoma (POAG) compared to those individuals not taking metformin; even after adjustment for diabetes control.

The aim of this PhD studentship is to understand the mechanisms through which metformin exerts a geroprotective effect in POAG to support the concept of drug-repurposing as a new therapeutic avenue for glaucoma.

To achieve this, we have four main objectives. These objectives will be achieved through the study of samples obtained from patients with POAG as this will (i) reflect the true human disease state and not rely on animal models which do not recapitulate the human condition; (ii) measure the effect of metformin on both local/ocular and systemic oxidative stress; and (iii) provide direct tissue samples to assess the effect and mechanism of action of metformin.

This are patient derived cells already available for study with ethical approvals in place and clinical collaborters to support the project in the Western and Belfast HSC Trusts.

These specific objectives map to the plan of investigation:

Objective 1. To determine the impact of metformin on the ocular and systemic oxidative status of POAG patients.

Objective 2: To investigate the mechanism of action of metformin in trabecular meshwork and Tenon’s fibroblast cells.

Objective 3: To determine the effect of metformin on trabecular meshwork and Tenon’s fibroblast cell function.

Objective 4: To determine the anti-fibrotic effects of metformin on trabecular meshwork and Tenon’s fibroblast cells.

This PhD project will provide the opportunity to generate a comprehensive dataset that will help move this novel glaucoma therapeutic from the pre-clinical to the clinical phase improving the treatment of glaucoma patients. Consumable funding is available to support this PhD.

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