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, passed from parents to their children), 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. Depending upon which part of the cornea is damaged, all or part of it can be replaced. However, like all organ donations, there is a shortage of donated eyes. Furthermore, as with any intraocular surgery, there are significant inherent risks, which include the potential of a blinding infection, or subsequent rejection or failure of the graft with time. After 10 years almost half of corneal transplants will have failed meaning that the patient will need another transplant. The risk of rejection increases with subsequent transplants. It is possible to remove a small number of corneal epithelial cells from a patient’s eye and grow sufficient numbers of them in the laboratory to transplant them back onto the eye. Our laboratory has shown it is possible to correct serious genetic defects within these cells while they are growing in the laboratory, allowing the patient’s own, now healthy normal cells to be placed back on the eye to restore vision.
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: CRISPR/Cas9 is a bacterial enzyme that can be used for genome engineering with unprecedented potential for gene therapy. Its advantage over previous technology is that it is easily reprogrammed, by simply changing a short stretch (20 bases) of RNA sequence, to cut DNA at different positions in the genome, depending on the target one wishes to edit. It can be used to knockout a gene, repair an error or direct the delivery of a therapeutic gene to a specified location. This project aims to test the ability of this enzyme to prevent the development of corneal disease using, as a model of corneal disease, mice which have been genetically engineered to develop different forms of the human disease. The ultimate aim of this study is to develop a safe and effective way to get this treatment to the cells that need it in the eye.
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.
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.Allen EH, et al. 2016. Keratin 12 missense mutation induces the unfolded protein response and apoptosis in Meesmann epithelial corneal dystrophy. Hum Mol Genet 25:1176.
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. 2014. siRNA silencing of the mutant keratin 12 allele in corneal limbal epithelial cells grown from patients with Meesmann's epithelial corneal dystrophy. IOVS 55:3352.
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.
6.Allen EHA, et al. 2013. Allele-Specific siRNA Silencing for the Common Keratin 12 Founder Mutation in Meesmann Epithelial Corneal Dystrophy. IOVS 54:494.
7.Liao H, et al. 2012. Development of allele-specific therapeutic siRNA in Meesmann epithelial corneal dystrophy. PLoS ONE 6:e28582
8.McLean WHI and Moore CBT. 2011. Keratin disorders – from gene to therapy. Hum Mol Genet 20(R2):R189.
9.Atkinson S, et al. 2011. Development of allele-specific therapeutic siRNA for keratin 5 mutations in epidermolysis bullosa simplex. J Invest Dermatol 131:2079
- To hold, or expect to achieve by 15 August, an Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC) in a related or cognate field.
- Sound understanding of subject area as evidenced by a comprehensive research proposal
- A comprehensive and articulate personal statement
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
The University offers the following awards to support PhD study and applications are invited from UK, EU and overseas for the following levels of support:
Vice Chancellors Research Studentship (VCRS)
Full award (full-time PhD fees + DfE level of maintenance grant + RTSG for 3 years).
This scholarship will cover full-time PhD tuition fees and provide the recipient with £15,000 maintenance grant 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.
Vice-Chancellor’s Research Bursary (VCRB)
Part award (full-time PhD fees + 50% DfE level of maintenance grant + RTSG for 3 years).
This scholarship will cover full-time PhD tuition fees and provide the recipient with £7,500 maintenance grant 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.
Vice-Chancellor’s Research Fees Bursary (VCRFB)
Fees only award (PhD fees + RTSG for 3 years).
This scholarship will cover full-time PhD tuition fees 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.
Department for the Economy (DFE)
The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £15,285 per annum for three years. EU applicants will only be eligible for the fee’s component of the studentship (no maintenance award is provided). For Non-EU nationals the candidate must be "settled" in the UK. 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.
Due consideration should be given to financing your studies; for further information on cost of living etc. please refer to: www.ulster.ac.uk/doctoralcollege/postgraduate-research/fees-and-funding/financing-your-studies
The Doctoral College at Ulster University
My experience has been great and the people that I have worked with have been amazing
Kieran O'Donnell - 3D printing of biological cells for tissue engineering applicationsWatch Video
Completing the MRes provided me with a lot of different skills, particularly in research methods and lab skills.
Michelle Clements Clements - MRes - Life and Health SciencesWatch Video
Throughout my PhD I’ve been provided with continuous support and guidance by my supervisors and the staff at the University.I’ve also received many opportunities to further enhance my professional development in the form of teaching experience and presenting my work at conferences which will aid in my pursuit of a career in academia or industry.