DRAM2: on the crossroad between trans-Golgi network and lysosomes?

This exciting project offers an opportunity for a motivated student to contribute to our understanding of retinal development and the impact of autophagy on retinal cell function. Obtaining this information will not only help to improve our understanding of retinal ageing, but also provide valuable information for the treatment of DRAM2 patients. Dysfunction and death of photoreceptors is thought to be the primary aetiology followed by retinal pigment epithelium (RPE) dysfunction in DRAM2 inherited retinal dystrophy; however how DRAM2 mediates this remains unknown. We will take a disease modelling approach by differentiating DRAM2 induced pluripotent stem cells to photoreceptors and RPE, which we will use to identify DRAM2 interacting proteins in both normal steady state and disease settings. The student will also perform DRAM2 tagging to better understand its processing and trafficking from endoplasmic reticulum to Golgi and the endosomal-lysosomal system. Last but not least, the student will supplement DRAM2 into photoreceptors and RPE cells to ascertain reversal of dysfunction and viability. These findings will be important for designing new therapeutic strategies for all the DRAM2 patients independent of the mutations.

The student will be based at the Newcastle University Biosciences Institute but will also spend several months working at the University of Durham and Radboud University, where they will perform yeast two-hybrid, co-immunoprecipitation, protein tagging, processing and trafficking experiments.

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, biochemistry 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.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with:

·        a CV (including contact details of at least two academic (or other relevant) referees);

·        a covering letter – clearly stating your first choice project, and optionally 2^nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]

The deadline for all applications is 12noon on Monday 9^th January 2023.