PhD Studentship - Transcriptional Profiling of Cell-specific Extracellular Vesicles in Solid Organ Transplantation

Applications are invited for a fully-funded 3-year studentship in the Department of Surgery at the University of Cambridge, under the supervision of Dr Vasilis Kosmoliaptsis. The posts will be based in the University of Cambridge Department of Surgery on the Cambridge.

Project title: Transcriptional profiling of cell-specific extracellular vesicles in solid organ transplantation

Extracellular vesicles (EVs) are membrane bound vesicles that are secreted into the extracellular space by most cell types; they are thought to reflect the conditional state of the parent cell and have emerged as important players in various physiological and pathological processes. A major interest of our lab is in investigating the role of EVs as mediators of inflammation during organ ischaemia-reperfusion injury and after transplantation. We are also interested in profiling EVs to develop biomarkers of the conditional state of donor organs. A major challenge in EV research is their inherent heterogeneity, such that the quantity and composition of EVs in complex biological samples reflect the activity of multiple cell types and the physiological state of the parent tissues.

The main focus of this studentship will be on developing methods for cell-specific EV detection and isolation from complex biofluids, such as human blood or urine. The investigation will capitalise on profiling of kidney, liver and cholangiocyte organoids, with paired EVs, under physiological conditions and under stress (such as hypoxia/reoxygenation). Further profiling of paired tissue and EVs will be performed using samples obtained during ex vivo perfusion of donor kidneys and livers representing various degrees of organ ischaemia-reperfusion injury. In addition, cell-specific EV profiling will be informed by EV isolation using bespoke EV aptamers developed in house. The objective of the studentship will be to build an atlas of cell-specific EVs at the transcriptomic level. A further objective will be to use single-cell RNA-seq data and transcriptional profiling of EVs released during ex vivo perfusion of donor organs to develop deconvolution algorithms that enable quantification of cell-specific EVs from bulk EV transcripts. The knowledge obtained from this investigation will be applied to understand the conditional state of donor organs during ex vivo perfusion and after transplantation with a focus on characterisation of the degree of organ inflammation and of organ injury.

What we are looking for:

This PhD studentship involves a combination of computational and wet lab research. Applicants should hold (or expect to obtain) the equivalent of a UK 2.1 or higher in an undergraduate honours or Masters degree in a relevant subject such as molecular biology, genetics or computational biology. The studentship is open to those eligible for the Home rate of University fees.

Fixed-term: The funds for this post are available for 3 years in the first instance.

Applications must be made via the University Applicant portal (Applicant Portal and Self-Service account ' Postgraduate Study (cam.ac.uk). Apply for 'PhD (Probationary) in Surgery' and then add 'PhD Studentship in Surgical Science' as the proposed project title, with Dr Kosmoliaptsis as the proposed supervisor.

Applications should include academic transcripts, CV, statement of purpose and two references.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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