Evaluate the Endothelial‐protective effects of a G‐protein‐biased sphingosine‐1 phosphate receptor‐1 agonists to reduce ischaemia reperfusion injury following transplantation

About the Project

A kidney transplant is the treatment of choice for patients with end-stage renal disease. There is both a scarcity of suitable organs for transplantation and a need to prolong their functionality after transplantation. Ischaemia reperfusion injury (IRI) and concomitant inflammation is associated with delayed graft dysfunction (DGF). One way to address this problem is to reduce the level of IRI to donor organs. There are currently no condition-specific therapeutics available. Sphingosine-1-phosphate receptor-1 (S1PR1) expressed on endothelial cells plays a fundamental role in maintaining barrier integrity.

 Our group has in vitro and in vivo data showing that agonism of S1PR1 can augment endothelial barrier function.  We aim to develop a G‑protein–biased S1PR1 agonist, that can be administered to the human donor kidneys during ex- vivo perfusion, protecting marginal organs and reducing DGF.

Our approach is comprehensive and multi-disciplinary and will bring together well-established Transplant immunology expertise with chemistry. It will equip the student to produce cutting edge research at the interface between chemistry and medicine. This project will utilise core research skills in cell biology, immunology, computational/medicinal chemistry etc. Utilising ex-vivo perfusion for organ directed reconditioning as a ‘drug delivery platform’ provides us with a unique opportunity to prevent or limit DFG. This fully funded studentship is available for outstanding candidates aiming to obtain high quality research training in an exciting and very translational subject area.

The Transplantation Research Group at NU supports one of the largest and most comprehensive clinical organ transplant programmes in Europe. Furthermore, NU co-hosts the NIHR-BTRU in partnership with Cambridge University (2022-2027, £4M). This unit is dedicated to improving ex-vivo organ assessment and maximising graft survival in the recipient. This will provide a world-class environment for training PhD students.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.