PhD Study : An Investigation into the role of Transforming Growth Factor-beta induced protein in corneal homeostasis and wound healing.

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Summary

Background to the project: When the clear window at the front of the eye, known as the cornea, is damaged by injury or disease (including hereditary genetic disease), it can become less transparent causing loss of sight and, at times, blindness. If the cornea becomes too damaged the only treatment available is a corneal transplant from a donor eye. Mutations in the transforming growth factor beta-induced (TGFBI) gene cause a group of inherited corneal dystrophies. Mutant TGFBI protein accumulates as opaque deposits in the extracellular matrix of the stroma and epithelium of the cornea affecting vision. Accidental injury or laser eye surgery accelerates the formation of these deposits; however, the exact molecular disease mechanisms remain unknown.

Methods to be used: The successful candidate will conduct cutting-edge research in state-of-the art facilities and gain wide experience in a variety of cell and molecular biology techniques. Samples from patients with and without corneal disease and established mouse models of corneal disease are already available. The student will join a group with both national and international collaborations that will allow pursuit of research towards the prevention of this debilitating disease.

Objectives of the Research: TGFBI protein expression increases in epithelial and stromal corneal cells near the wound in injured normal cornea. In preliminary experiments, we have shown that inhibition of TGFBI expression slows tissue regeneration in a zebrafish model. This project aims to test the hypothesis that normal TGFBI protein is necessary for the wound healing process in the cornea. CRISPR/Cas9 is a bacterial enzyme that can be used for genome engineering. We propose to use CRISPR/Cas9 to obtain TGFBI-null corneal cell lines and study responses to injury. We have shown that it is possible to use CRISPR/Cas9 to knockout gene expression in mouse cornea and this project will investigate the wound healing response of corneas deficient in TGFBI. This project aims to test the ability of CRISPR/Cas9 to prevent the development of corneal disease using a mouse model which has been genetically engineered to develop TGFBI corneal dystrophy.

Skills required of applicant: The applicant should have experience of undertaking a research project, good communication and organisational skills, experience of effective team working and an ability and willingness to learn new skills and techniques, undertake scientific writing and to travel.

Applications are welcomed from both medical and non-medical graduates.

References:

1.Christie KA et al. 2017. Towards personalised allele-specific CRISPR gene editing to treat autosomal dominant disorders. Sci Rep Nov 22; 7(1):16174. doi:10.1038/s41598-017-16279-4

2.Chao-Shern C et al. 2017. Post-LASIK exacerbation of granular corneal dystrophy type 2 in members of a Chinese family. Eye in press

3.Courtney DG, et al. 2016. CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting. Gene Ther 23:108

4.Courtney DG, et al. 2015. Protein Composition of TGFBI-R124C- and TGFBI-R555W-Associated Aggregates Suggests Multiple Mechanisms Leading to Lattice and Granular Corneal Dystrophy. IOVS 56:4653.

5.Courtney DG, et al. 2014. Development of allele-specific gene-silencing siRNAs for TGFBI Arg124Cys in lattice corneal dystrophy type I. IOVS 55:977.

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
  • 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
  • Masters at 65%
  • 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 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

The Doctoral College at Ulster University

Key dates

Submission deadline
Monday 19 February 2018
12:00AM

Interview Date
6, 7 and 8 March 2018

Preferred student start date
Mid September 2018

Applying

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Contact supervisor

Dr Andrew Nesbit

Other supervisors