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PhD studentship: Exploring the mechanisms of Acute Kidney Injury (AKI) using a novel in vitro culture system


Division of Medicine

About the Project

Ref: 1871185

Division of Medicine
Research Department of Renal Medicine
London
Duration of Studentship: 3 years
Stipend: 2020/21: £17,285; 2021/22: £17,631; 2022/23: £17,983

Acute Kidney Injury (AKI) as a result of ischaemia-reperfusion injury (IRI), is a common cause of kidney damage especially in older individuals. In many forms of AKI, infiltrating pro-inflammatory macrophages are critical mediators of tubular damage. Repeated episodes of AKI can lead to, or exacerbate, chronic kidney disease (CKD), and effective therapies for treatment or prevention are lacking. Most research into AKI is based on in vivo rodent models of IRI, which are poor at replicating human risk factors (e.g. ageing, diabetes and pre-existing CKD). As a result there has been a striking failure of promising pre-clinical targets to translate to clinical efficacy and there is a pressing need for alternative models to better understand AKI.

The aim of the proposed study is to develop, characterize, and validate a novel in vitro model based on human kidney cells co-cultured with macrophages under conditions mimicking ischemia reperfusion, to provide new insights in the pathobiology of macrophage-tubular cell interactions in AKI. Interesting novel findings will be validated using an ex vivo co-culture system based on human kidney tissue slices and macrophages. This will also provide novel platforms for testing new therapeutics.

Based in the Division of Medicine - Research Department of Renal Medicine, the student will have the opportunity to work with leading academics and clinicians. The studentship is funded by the St Peters Trust and there will be opportunity for the student to access a wide range of scientific platforms and technologies. Any new therapeutic outcome in our models that attenuates injury could be further developed for clinical application through existing collaborations with the pharmaceutical industry.

Studentship Description
Human proximal tubular cells in transwell co-culture with macrophages will be evaluated under conditions mimicking IRI in clinically-relevant scenarios viz. repeated injury, diabetes and aging. Cellular responses will be assessed for established markers of cell injury using a range of techniques, including LNA GapmeR RNA silencing, qPCR, RNASeq, fluorescence-activated cells sorting (FACS), confocal microscopy and multiplex secretome analysis. In particular, the importance of non-coding RNAs such as long non-coding RNAs (LncRNAs) in renal IRI will be investigated. Novel findings will be validated in precision cut human kidney slices. Bioinformatical analyses including RNA interactome analysis, will be performed and data compared with published human, pre-clinical and in vitro data sets to provide a better understanding of the pathophysiology of IRI. In addition, the models will be validated as platforms for therapeutic testing of novel compounds.

For more information regarding the project and the research group, please contact: and visit the UCL website https://www.ucl.ac.uk/nephrology/.

Applications should sent directly to Dr Enriko Klootwijk () and include a Curriculum Vitae (CV) and a cover letter. This should set out your previous academic or other experience relevant to the proposed research; why you wish to undertake this research at UCL; your previous research or professional training and what further training you think you will need to complete a PhD; and what ethical issues you will need to consider in undertaking this research. In addition, two references should be named at the end of the statement. At least one reference must be from an academic referee who is in a position to comment on the standard of your academic work and suitability for postgraduate level study. Where appropriate, a second referee can provide comment on your professional experience.

Person Specification
Applicants must have obtained at least an upper second-class honours degree (2:1, or equivalent qualification) in a relevant subject. They would be required to have an interest in renal pathophysiology, cell and molecular biology and bioinformatics. Applicants are expected to be highly motivated to pursue a PhD in medical sciences and are required to work as part of a team.

Practical experience in a relevant subject would be an advantage, although it is not essential. Some experience in programming (e.g. C+, C++, python, or R) and/or RNA sequence analysis would also be desirable.

Eligibility


Eligibility criteria for UCL research degrees can be found at:
https://www.ucl.ac.uk/prospective-students/graduate/research-degrees/entry-requirements

Closing Date: 30th November 2020 at 23.59
Interview Date: To be confirmed

Please note: Applications from candidates who are not eligible will not be considered.

UCL Taking Action for Equality

This role does not meet the eligibility requirements for a tier 2 certificate of sponsorship under UK Visas and Immigration legislation. Therefore, UCL will not be able to sponsor individuals who require right to work in the UK to carry out this role.


Funding Notes

This funding is limited to UK/EU nationals and is for 3 years. The stipend amount will be 2020/21: £17,285, 2021/22: £17,631, 2022/23: £17,983 plus Home/EU fees and consumables.

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