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

This opportunity is now closed.

Subject: Biomedical Sciences

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

  • 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
  • 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

    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

Launch of the Doctoral College

Current PhD researchers and an alumnus shared their experiences, career development and the social impact of their work at the launch of 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

Dr Andrew Nesbit

Other Supervisors

Apply online

Visit https://www.ulster.ac.uk/applyonline and quote reference number #238265 when applying for this PhD opportunity