PhD Study : Novel hydrogel delivery platforms for quadruplex stimulation of fibroblast activity in chronic ulceration.

Apply and key information  

Summary

Chronic wounds represent a significant burden to patients with recent data confirming some 200,000 patients in the UK being affected.  The cost to the NHS of caring for patients with a chronic wound is conservatively estimated to be approximately £4.5bn–5.2bn per year. (1) Chronic wounds can be classified as vascular ulcers (e.g., venous and arterial ulcers), diabetic ulcers and pressure ulcers. Some common features shared by each of these wounds include prolonged or excessive inflammation, persistent infections, formation of drug-resistant microbial biofilms and the inability of dermal and/or epidermal cells to respond to reparative stimuli.

Chronic wounds are characterised by senescent cell populations with impaired proliferative and secretory capacities, rendering them unresponsive to typical wound healing signals. It has been reported that fibroblasts from venous and pressure ulcers are senescent and have a diminished ability to proliferate. This diminished proliferative capacity is directly correlated with the failure of a wound to heal. (2,3)

Underlying aim

Recent published data reveal a clear link between G‐quadruplex DNA formation in TGF‐β‐stimulated primary human fibroblasts, leading to accelerated extracellular matrix depositions. (4)

This raises the possibility that therapeutic application of G‐quadruplex DNA to senescent fibroblasts in the wound bed could initiate collagen formation and overcome healing stasis and offer a potential alternative to current interventions.

Specific objectives/Methodology objectives

  • To formulate and characterise shear-responsive hydrogels, loaded with test G‐quadruplex DNA
  • To evaluate stability, release kinetics and bioavailability
  • To evaluate fibroblast motility and collagen synthesis following stimulation using tissue factors and G‐quadruplex DNA Methods

This project will involve formulation of a novel, G‐quadruplex DNA-loaded hydrogel, followed by a detailed characterisation of drug stability and release kinetics.  Changes in rheological profiles will be determined using oscillating rheometry.  Immunohistochemical staining for will be used to determine collagen 1 visualisation in fibroblast populations.  In order to visualise the presence of DNA and RNA G‐quadruplex in cells, immunofluorescence using a G‐quadruplex structure‐specific antibody (BG4), which enables visualisation of pre‐existing G‐quadruplexes in human cells, will be used.  The motility of fibroblasts following exposure to G‐quadruplex DNA will be determined using a scratch assay and proliferation across an induced void will be measured and compared to normal fibroblasts.

Requisite experience

The applicant must possess a first class or upper second class honours degree in a science subject or health science subject (e.g. Pharmacy, Pharmaceutical Biosciences, Biomedical Sciences, Chemistry, Biology). Previous experience of cell culture would be desirable.

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

Recommended reading

1. Turner N, Ovens L. The results of a clinical evaluation of Accel-Heal® electroceutical treatment in a large NHS Trust. Wounds UK 2017;13:92-99.

2. Stanley A, Osler T. Senescence and the healing rates of venous ulcers. J Vasc Surg 2001;33:1206–1211.

3. Lobmann R, Ambrosch A, Schultz G, Waldmann K, Schiweck S, Lehnert H. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia 2002;45:1011–1016.

4.  Toshniwal P,  Nguyen M. TGF‐β‐induced fibrotic stress increases G‐quadruplex formation in human fibroblasts.  FEB Letters 2019;593:3149-3161.

The Doctoral College at Ulster University

Key dates

Submission deadline
Friday 5 February 2021
12:00AM

Interview Date
Weeks Commencing 15th and 22nd March 2021

Preferred student start date
Mid-September 2021

Applying

Apply Online  

Contact supervisor

Professor Paul McCarron

Other supervisors