RetinaUK/Macular Society-funded 3 Year PhD Studentship

Project title: Deciphering RPGR’s role in disc formation

Application deadline: 21st June 2023

Funding information (students eligible to apply) – This studentship is jointly funded by RetinaUK and the Macula Society; UK & International students are eligible to apply.

The aim of this PhD will be to define the role of RPGR in retinal cone photoreceptors, and the effects of human RPGR mutations on cone function. It will be carried out at the MRC Human Genetics Unit at the University of Edinburgh.

Inherited retinal disorders (IRDs) are the leading cause of visual loss in children and working adults in the UK. Mutations in one of over 280 genes lead to death of the light sensing photoreceptors at the back of the eye. A lack of understanding of the role these genes play in retinal health mean the vast majority remain untreatable. RPGR is a leading causal IRD gene and a subset of human RPGR mutations cause cone photoreceptor death, leading to early onset loss of central vision. Determining its role in cone function is therefore crucial if we are to develop therapies.

Our lab uses a novel Rpgr mouse model which undergoes early loss of cone function, making it an ideal model to better understand the role of RPGR in cone function. During this PhD, the student will use this humanised model, crossed to a cone reporter mouse, to isolate mutant cones for bulk RNA sequencing experiments. These datasets will be interrogated to understand how Rpgr’s role in cones and how cones die in disease. They will learn the novel technique, ultra-structure expansion microscopy, in order to better define structural changes in diseased cones. They will overexpress human RPGR constructs in cell lines to test their function in photoreceptor maintenance. 

By the end of the PhD, students will have developed a broad skillset, including large dataset analysis, advanced imaging techniques, molecular biology and both cell and animal work. They will have developed an excellent research network thanks to an international placement and presentations at leading conferences. They will have undertaken public engagement projects, giving them ties to the patient community.

Want to discuss further, email inquiries can be made to Roly or Pleasantine directly.