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

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.

Eligibility:
This project is available immediately to both Home/EU rate applicants and International applicants who are able to self-fund their studies. Students 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 formal apply for this project applicants should complete a Faculty Application form using the link below https://medicinehealth.leeds.ac.uk/downloads/download/78/fmh_scholarship_application_form_2018_2019 and send this alongside a full academic CV, degree certificates and transcripts (or marks so far if still studying) to the Faculty Graduate School at [Email Address Removed]

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

Any queries regarding the application process should be directed to [Email Address Removed]

Potential applicants are welcome to contact Dr Carmel Toomes at [Email Address Removed] with informal enquiries about this research project.