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MRC DiMeN Doctoral Training Partnership: Ex-vivo normothermic perfusion of organs to minimise ischemia reperfusion injury


Project Description

Transplantation is the gold-standard treatment for patients with end stage diseases. However, the supply of donor organs is limited in number and quality. Ischaemia reperfusion injury (IRI)at the time of lung transplantation may lead to primary graft dysfunction (PGD) in the recipient. PGD carries a significant early mortality risk of ~30% and is also associated with poorer long term outcomes. There is no disease-specific therapeutics available to treat the condition.

The Newcastle transplant group has developed a programme of ex-vivo lung perfusion (EVLP). The use of EVLP provides a unique opportunity to further improve our understanding of leucocyte – endothelial cell interactions underlying IRI and to study how novel therapeutics might ameliorate the innate immune cascade. Our group has already developed important pilot data showing that agonism of sphingosine-1-phosphate (S1P) receptors can augment endothelial barrier function. In this project we will use EVLP to a) modify the potential for leucocyte-vascular endothelium interaction and b) restore the integrity of the vascular permeability barrier to limit the risk of early graft injury. The overall aim of this project is to develop and evaluate novel approaches and technologies that increase the availability of donor organs for human transplantation, while also improving survival of the transplanted organ.

Our approach is comprehensive and multi-disciplinary and will bring together well-established clinical expertise with basic science and industry collaboration (XVIVO, Sweden). XVIVO is a leading company within the field of transplantation. Our Industry collaborators will provide a secondment opportunity, during which the student will gain experience of working across the sector. This project will utilise core research skills in cell biology, immunology, cell migration, flow based adhesion, RNA Seq etc. Utilising EVLP for organ directed reconditioning as a ‘drug delivery platform’ provides us with a unique opportunity to prevent or limit PGD. This fully funded studentship is available for outstanding candidates aiming to obtain high quality research training in an exciting and very translational subject area.


For further information about these studentships please contact:
Professor Simi Ali () https://www.ncl.ac.uk/icm/people/profile/simiali.html#background
Professor Andrew Fisher ()
https://www.ncl.ac.uk/icm/people/profile/ajfisher.html#background
Anne-Li Sigvardsson (XVIVO, Sweden), Http://www.xvivoperfusion.com/

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 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: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

iCASE Award: Industrial partnership project
Fully funded by the MRC for 3.5yrs, including a minimum of 3 months working within the industry partner. Enhanced stipend, tuition fees and budget for consumables, travel and subsistence.
Studentships commence: 1st October 2019.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website
Good luck!

References

1. Andreasson ASI, Borthwick LA, Gillespie C, Jiwa K, Scott J, Henderson P, Mayes J, Romano R, Roman M, Ali S, Fildes JE, Marczin N, Dark JH, Fisher AJ, on behalf of the DEVELOP-UK Investigators. The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion. Journal of Heart and Lung Transplantation 2017, 36(9), 985-995.

2. Barker CE, Thompson S, O'Boyle G, Lortat-Jacob H, Sheerin NS, Ali S, Kirby JA. CCL2 nitration is a negative regulator of chemokine-mediated inflammation. Scientific Reports 2017, 7, 44384.

3. Ladak SS, Ward C, Ali S. The potential role of microRNAs in lung allograft rejection. Journal of Heart and Lung Transplantation 2016, 35(5), 550-9.

How good is research at Newcastle University in Clinical Medicine?

FTE Category A staff submitted: 147.13

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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