Our previous work on the genetic analysis of individuals with the inherited retinal disease Familial Exudative Vitreoretinopathy (FEVR), has helped identify a new angiogenesis pathway, the Norrin/beta-catenin pathway. This pathway shares a lot of similarity and components with the well-characterized WNT/beta-catenin signaling pathway but Norrin is the ligand instead of WNT. The aim of this project is to characterize this pathway by identifying new components and functionally characterizing how the different elements of this pathway interact.
We aim to undertake high-throughput gene knockdown screens based on luciferase reporter outputs to identify pathway components. This will require creating a suitable cell line for the screen using CRISPR gene editing, optimizing and performing the screen and validating positive hits. Further analysis will involve studying the best hits to characterize their position in the pathway and their interactants. Finally, there are still up to 40% of FEVR patients without a molecular diagnosis so any hits will be analyzed in whole genome sequences of unsolved FEVR cases to try and identify new disease genes.
Techniques associated with this project:
The student will gain experience in a wide range of state-of-the-art approaches in biomedical research including CRISPR, high-throughput screening, real time PCR, western blotting, confocal imaging, RNA sequencing/data analysis, protein interaction assays like BioID and Duolink proximity ligase assays, and whole genome sequence analysis.
This project is part of the International PhD Academy: Medical Research
Eligibility:
You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject.
Candidates 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 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.
How to apply:
Applications can be made at any time. To apply for this project applicants should complete an online application form and attach the following documentation to support their application.
- a full academic CV
- degree certificate and transcripts of marks
- Evidence that you meet the University's minimum English language requirements (if applicable)
To help us identify that you are applying for this project please ensure you provide the following information on your application form;
- Select PhD in Medicine, Health and Human Disease as your programme of study
- Give the full project title and name the supervisors listed in this advert
Any queries regarding the application process should be directed to fmhpgradmissions@leeds.ac.uk
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