LIMR Genetics: Genetic studies of developmental eye disorders to investigate genotype-phenotype correlations

Summary

Developmental eye defects that affect the front of the eye give rise to a spectrum of congenital ocular phenotypes that affect the cornea, lens, iris, trabecular meshwork or the globe itself. They can be non-syndromic affecting the eye only or the condition may be associated with systemic features. Patients sometimes present with distinct phenotypes that are easy to diagnose or they may have multiple signs with considerable overlapping features that makes accurate diagnosis more difficult. Knowing the genetic basis of these conditions helps to classify the patients into definitive disease categories.

The primary aim of this project will be to identify the molecular basis of congenital eye disease in multiple local cases. Whole genome sequencing (WGS) and whole exome sequencing (WES) of these cases will identify coding and non-coding variants both in known and novel genes that have not been previously implicated in the disorder. 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 improve management and support the development of new therapies for these rare conditions.

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.

In line with the bespoke nature of our International PhD Academy a modified PhD project can be proposed dependent on students interests and background.

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The minimum requirements fpr this programme in IELTS and TOEFL tests are: • British Council IELTS - score of 7.0 overall, with no element less than 6.5 • TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.