Physiology and biological impact of removing circulating cell-free DNA/Neutrophil Extracellular Trap (cfDNA/NET) on modifying lung injury at University of Edinburgh on FindAPhD.com

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Prof Manu Shankar-Hari, Prof Kev Dhaliwal No more applications being accepted Competition Funded PhD Project (Students Worldwide)

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Edinburgh United Kingdom Cancer Biology Immunology Microbiology

About the Project

· Background

In critically ill patients, cell free DNA (cfDNA), a danger signal capable of initiating intense innate immune responses, is measurable in circulation. Higher levels of cfDNA in circulation is associated with greater inflammatory responses. Ex vivo lung perfusion (EVLP) is a technique that maintains lung function for possible transplantation after organ donation. We have access to human lungs unacceptable for transplant and we have the know how to model endotoxemic injury with EVLP for 6 hours. EVLP models provide a pre-clinical platform for assessment of potential interventions that may either increase the lung suitable for transplant or may reduce the severity of lung injury in critically ill patients.

· About the Project

In this context, we hypothesise that removal of circulating cell-free DNA/Neutrophil Extracellular Traps (cfDNA/NET) will improve lung physiology, primarily by modulating the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway. Using human ex vivo lung perfusion (EVLP) models (in non-transplantable lungs and in injured lungs (direct and indirect LPS injury)), compare the baseline and 4-hour post cfDNA/NET blood purification,

o Physiology, macroscopic, and microscopic changes to lung

o immune and lung parenchymal cell phenotypic and molecular changes in the cGAS-STING pathway and inflammasome pathways.

o Markers of inflammation and injury in the perfusate and lavage fluid.

The research group is located in the University of Edinburgh Centre for Inflammation Research; a world-class research environment at the interface between biological and medical science, with multidisciplinary groupings focused on inflammation, infection, disease and repair. The Centre is based within the Edinburgh Medical School in the outstanding facilities of the Queen’s Medical Research Institute at the site of the Royal Infirmary of Edinburgh hospital, maximising future translational opportunities.

As part of the application process, please fill and submit the online application form.

Funding Notes

The successful applicant will be awarded a 4 year studentship, which includes their stipend (£19,000 per annum), tuition fees, and contributions towards travel and research costs for their PhD project.
The studentship will be awarded competitively. Applicants should hold at least an upper second class degree or equivalent in a relevant discipline (eg immunology, or biology). Applicants should submit the following documents: (i) Personal statement about their research interests and their reasons for applying; and (ii) CV.

References

Applicants should also arrange for two academic referees to submit letters of reference via email before the deadline , including "Reference for [applicants’ name] M S-H PhD" in the subject.
All documents should be submitted to CIR.Postgraduate@ed.ac.uk no later than 5pm on 25th February 2022.
Short-listed candidates will be notified by email.
Informal enquiries can be sent via email to Prof Manu Shankar-Hari (manu.shankar-hari@ed.ac.uk)