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Developing an ex vivo tissue slice model of injured kidney to analyse how immune cells and ageing influence the endogenous regenerative response


Faculty of Health and Life Science

Dr B Wilm , Prof Neil Sheerin , Dr J Coombes Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Liverpool United Kingdom Biomedical Engineering Cell Biology Immunology

About the Project

In acute kidney injury, renal tubular cells are damaged and inflammatory cells are recruited to resolve the injury by helping to restore the local tissue environment. However, if inflammatory cells fail to resolve the injury, this leads to myofibroblast activation, deposition of collagen and build-up of fibrosis. In aged kidneys, the resolution of the inflammation is delayed. By contrast, paracrine factors released by mesenchymal stromal cells acting as regenerative medicine therapies can modulate the inflammatory response and lead to resolution by promoting anti-inflammatory immune cells. How this endogenous regenerative process is regulated across different age groups, and how the inflammatory response can be modulated either in ageing, or through therapeutic intervention, is not well understood. Specifically, the interplay between inflammatory cells, damaged kidney cells and cytokines needs further detailed analysis, which can serve as an exemplar for processes of tissue inflammation and resolution in other organs systems.

 

In this BBSRC-funded PhD project at the University of Liverpool, the appointed PhD student will be trained in establishing an ex vivo precision cut kidney slice (PCKS) model from mouse to use as a novel test-bed to analyse the response of resident and recruited inflammatory cells to injury in young adult and aged kidneys. The student will optimise PCKS culture during a secondment at the Newcastle Fibrosis Research Group at Newcastle University, the partner university for this BBSRC PhD studentship. The PCKS culture system will then be implemented at the University of Liverpool, allowing the student to address a range of aims including:

  1. Determining how the interactions of immune cells with the damaged cells, and cytokines released, influence the resolution of inflammation in young adult and aged kidneys;
  2. Understanding the basis for delayed resolution of inflammation in kidneys of aged mice;
  3. Analysing how paracrine factors released by cell therapies modulate the behaviour of inflammatory/immune cells and their role in inflammation resolution.

The student will receive training in in vivo techniques, including surgery to induce renal ischaemia reperfusion injury in mouse and other important in vivo skills. The project will provide the student with a highly sought-after skill set including flow cytometry, cytokine analysis, characterisation of tissue integrity, and confocal microscopy. The student will be embedded in a vibrant research group focussed on various aspects surrounding the processes of endogenous renal injury regeneration and the role of immune cells and cytokines in renal repair. The BBSRC welcomes application from students from diverse backgrounds.

HOW TO APPLY

Applications should be made by emailing with a CV and a covering letter. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.


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