Genetic studies of corneal endothelial dystrophies and development of alternative treatment options

Project description

The cornea is the protective front part of the eye that provides most of the eyes focusing power. The endothelium is a single-cell layer on the inside of the cornea that maintains fluid balance and is required for corneal transparency. The late-onset inherited eye condition, Fuchs endothelial corneal dystrophy (FECD), which is the most common cause of corneal transplantation, affects 5% of people over 40 years old who develop blurred vision as a result of endothelial dysfunction and could lead to blindness. About 70% of cases are caused by a trinucleotide repeat expansion in the intron of TCF4, which causes RNA nuclear foci to develop in the patient’s endothelial cells that leads to cell death. Mendelian mutations in SLC4A11, ZEB1, LOXHD1 and AGBL1 only account for at most 5% of cases leaving about 25% of cases with unidentified mutations.

The primary aim of this project will be to identify the cause of FECD in those cases in whom the mutations have not yet been discovered by initially selecting those with a clear family history. Whole genome sequencing (WGS) and whole exome sequencing (WES) of these cases will identify coding and non-coding variants both in the known FECD genes and in novel genes. These variants will be further studied to provide functional validation of the genetic findings but specific experiments will be determined by the initial findings. Better understanding of the disease mechanisms in light of the molecular diagnosis will support the development of new therapies for this condition.

The techniques used in this PhD will include bioinformatics, analyzing WES and WGS data, PCR, Sanger sequencing, functional validation of variants may include expression profiling, spicing mini- and midi-gene assays, protein structural modelling, RNA sequencing, creating knock-out cell models of putative pathogenic variants by CRISPR-Cas9 genome editing and the study of animal models where available. The search for therapies would include a high throughput small molecule screen with functional readout where that is available.

Entry requirements

This project is available immediately to both Home/EU rate applicants and International applicants who are have a sponsor or are able to self-fund their studies. You must be able to provide the appropriate level of fees based on their fee status plus laboratory consumables costs per year. This is in addition to the provision of personal living expenses.

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject.

Candidate whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are:

•      British Council IELTS - score of 6.5 overall, with no element less than 6.0

•      TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

Applicants with sufficient funding must still undergo formal interview prior to acceptance in order to demonstrate scientific aptitude and English language capability.

How to apply

Applications can be made at any time. To apply for this project applicants should complete a Faculty Scholarship Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to

If you have already applied for other scholarships using the Faculty Scholarship Application form this academic session you do not need to complete this form again. Instead you should email to inform us you would like to be considered for this scholarship project.

Any queries regarding the application process should be directed to

How to apply (email)