Funded PhD Opportunity MicroRNA-based Therapeutics for Fibrosis in Glaucoma.

This opportunity is now closed.

Subject: Biomedical Sciences

Summary

Glaucoma is a major cause of irreversible blindness, affecting more than 60 million people worldwide increasing to an estimated 79.6 million people by 2020. Primary open-angle glaucoma (POAG) is the commonest type of glaucoma and intraocular pressure (IOP) is an important modifiable risk factor. Elevated IOP in POAG is due to increased resistance to aqueous humour outflow and is the only treatable risk factor for glaucoma. Elevated IOP results from increased aqueous humour outflow resistance, a result of several morphologic and biochemical changes in the trabecular meshwork (TM); changes in the number of TM cells and the extracellular matrix (ECM) within the TM.  There is a large body of evidence that transforming growth factors - β1 and - β2 (TGF-β1 and -β2) play an important role in the pathogenesis of POAG. As well as playing a fundamental role in the pathogenesis of POAG by altering TM function and outflow facility and elevating IOP, TGFβ also has a deleterious effect on surgical outcomes for glaucoma causing post-operative scarring and surgical failure. MicroRNA (miRNA) based manipulation of the TGFβ signalling pathway is a new approach to target fibrosis following glaucoma surgery. MicroRNAs are small, non-coding RNAs which are important regulators of eukaryotic gene expression in most biological processes. miRNA-based therapeutics is an emerging field which is beginning to enter the clinical arena. In preliminary studies using genome-wide micro-arrays and small RNA-Seq we have identified miRNAs which are upregulated following TGFβ treatment of TM cells; we have termed ‘GlaucoMirs’. The specific impact of manipulating these ‘GlaucoMirs’ on the TGFβ signalling pathway could herald the generation of a new class of therapeutics for the medical and surgical management of glaucoma.

The aim of this studentship is to develop microRNA-based therapeutics to control fibrosis in glaucoma. A number of human and animal (porcine/bovine) cell and tissue models are available to support this project. We have an established ex vivo glaucoma perfusion model which the student will validate using porcine and/or bovine eye and utilise to perform microRNA manipulations to determine therapeutic endpoints. This ex vivo organ culture model which maintains the anterior segment of a pair of porcine/bovine eyes and glaucoma (raised IOP) is induced with TGFβ infusion in one eye; the untreated eye remains as control. miRNA mimics or inhibitors can be perfused to rescue IOP and downstream evaluation of mRNA, protein and structure can be evaluated directly in the TM. Drug delivery and efficacy can also be tested.

The specific objectives are: (1) Establish and validate a porcine and/or bovine glaucoma perfusion model. (2) Confirmation and identification of ‘GlaucoMirs’ using bioinformatics data mining and analyses combined with miRNA qPCR. (3) Experimental validation of miRNA targets. (4) Therapeutic manipulation of miRNAs as a phenotypic rescue to control fibrosis in glaucoma.

Essential Criteria

  • Upper Second Class Honours (2:1) Degree from a UK institution (or overseas award deemed equivalent via UK NARIC)
  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • A comprehensive and articulate personal statement

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.

  • First Class Honours (1st) Degree
  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Research project completion within taught Masters degree or MRES
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings

Funding

    Vice Chancellors Research Scholarships (VCRS)

    The scholarships will cover tuition fees and a maintenance award of £14,777 per annum for three years (subject to satisfactory academic performance). Applications are invited from UK, European Union and overseas students.

    DFE

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 14,777 per annum for three years. EU applicants will only be eligible for the fees component of the studentship (no maintenance award is provided).  For Non EU nationals the candidate must be "settled" in the UK.

Other information

The Doctoral College at Ulster University

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Key Dates

Submission Deadline
Monday 19 February 2018
Interview Date
6, 7 and 8 March 2018

Contact Supervisor

Professor Tara Moore

Other Supervisors

Apply online

Visit https://www.ulster.ac.uk/applyonline and quote reference number #238269 when applying for this PhD opportunity