LIMR Genetics: Unravelling the Norrin/beta-catenin signaling pathway and its role in retinal angiogenesis and blindness

Summary

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

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. 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 for 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.