Using next-generation sequencing and CRISPR-Cas9 gene editing to investigate penetrance and phenotypic variation in inherited eye disease

Summary

Human inherited retinal diseases (IRDs) result from mutations in over 250 different genes, many of them implicated by the Leeds Vision Research Group (eg Panagiotou et al 2017, AJHG 100:960-968; El-Asrag et al 2015, 96:948-54). While these discoveries have greatly increased our understanding of the proteins and pathways underlying these disorders, we know very little about the molecular processes which underlie the huge variation in symptoms and severity seen between individuals. In its most extreme form, some primary mutation carriers have no symptoms while other family members with the same mutation are blind from infancy. Understanding the causes of this variability will allow accurate counselling and molecular testing of IRDs and will facilitate the development of therapies for IRDs and other common complex eye disorder.

It is commonly accepted that this variability in penetrance and disease expression is governed at least in part by secondary genetic factors. This project will aim to identify these genetic modifiers and functionally validate then using in in vitro cellular systems. This project will provide research training in genomics and cell biology including the bioinformatics analysis of whole exome/genome sequencing, cell culture, gene editing, siRNA/shRNA gene knockdown and microscopy.

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 Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD 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.