MRC DiMeN Doctoral Training Partnership: Understanding the molecular mechanisms of photoreceptor and choroid endothelial cell death in age related macular degeneration

This exciting project offers an opportunity for a motivated student to contribute to our understanding of fundamental pathomechanisms leading to age-related macular degeneration (AMD). Obtaining this information will not only help to improve our disease understanding, but also provide valuable information for regenerative medicine and drug discovery studies. Dysfunction and death of retinal pigment epithelium (RPE) cells is thought to be the primary cause of AMD; however death of photoreceptors and choroid endothelial cells (CECs), occurs secondary to the RPE. While a lot is known about RPE dysfunction, mechanisms surrounding photoreceptor and CECs death are unclear and to date is not known whether these are related to RPE cell death or due to an intrinsic defect in these cell types. We will take a disease modelling approach by differentiating AMD patient specific induced pluripotent stem cells to photoreceptors and CECs, which would allow us to identify cell intrinsic defects independent of RPE dysfunction. These findings will be important for designing new therapeutic strategies for AMD and defining new biomarkers for early diagnosis.

The student will be based at the Newcastle University Biosciences Institute (http://www.retinalstemcellresearch.co.uk/), but will also spend several months working at the University of Liverpool (https://www.liverpool.ac.uk/life-course-and-medical-sciences/staff/rachel-williams/) and

Queen’s University Belfast (https://pure.qub.ac.uk/en/persons/reinhold-medina),

where they will learn cell death, oxidative stress and waste disposal assays as

well be trained in differentiation to CECs and their characterisation.

Newcastle University has invested in stem cell research across its research institute. It provides excellent support to encourage cross-disciplinary research, including access to high specification equipment. Human embryonic and foetal eye tissue is available through existing collaborations with Human Developmental Biology Resource.

All postgraduate research students (PGRs) undertake formal, personalised training at Newcastle University. This creates a learning environment that allows PGRs to enhance their skills for a successful research experience and career. Specific to this project is strong clinical interaction with both healthcare professionals and patients, via RVI Newcastle Eye Department and Sunderland Eye Infirmary. Participation in public and patient engagement events, for which the host department have won awards, is strongly encouraged.

This project would be suited to a candidate with a Bachelor or Master’s degree in stem cell research, neuroscience, regenerative medicine, or ageing. Knowledge of eye/retinal development is desirable but not essential. Upon completion, the candidate will have developed into a professional stem cell biologist capable of using iPSC-based disease models to generate knowledge underpinning fundamental biological questions that could help solve complex clinical problems.

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: https://www.dimen.org.uk/blog

Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/how-to-apply