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Extracellular vesicles as indicators of immune status and outcome in sepsis patients


Project Description

Sepsis is a major health care burden with unacceptably high rates of mortality. The underlying pathogenic mechanisms are multifactorial involving dysfunctional immune and metabolic responses to infection. Recent studies assessing gene expression (transcriptome/proteome) patterns in patient blood samples have identified distinct phenotypes (‘sepsis response signatures’) that are predictive of poor outcome (1). Such findings advance our progress toward personalised medicine for sepsis, but successful implementation will require practical and accurate methods for screening patient samples.

This project is part of the NIHR-funded initiative at Imperial College to develop personalised medicine in sepsis. The aims of this specific project are to determine the utility of extracellular vesicles (EVs) for evaluation of immune status in sepsis patients. EVs are lipid-encapsulated particles produced by all cells and present in body fluids, including blood and urine (2). They contain diverse molecular cargoes (proteins, nucleic acids and lipids) that form a biosignature of the parent cell, as well as endowing functions related to inflammation and immunity. We have recently demonstrated that EVs can provide both diagnostic and prognostic information in sepsis and major trauma patients (3, 4). The overall aims of the project are to: (1) enhance and refine existing methodologies for rapid isolation of EV subtypes; (2) assess the relationship between MV subtype cargo and sepsis severity; (3) determine overall feasibility and potential advantages of EV-based analysis over existing patient phenotyping approaches.

The successful candidate will form part of the team of both clinical and laboratory scientists undertaking a range of translational research studies in sepsis.

Funding Notes

Funded by the National Institute for Health Research (NIHR). The studentship is part of a full-time Research Assistant position for 33-36 months with all fees included.

References

1. Davenport EE et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016;4(4):259-71.
2. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373-83.
3. Herrmann IK et al. Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation. Nanoscale. 2015;7(32):13511-20.
4. O'Dea KP et al. Circulating Microvesicles Are Elevated Acutely following Major Burns Injury and Associated with Clinical Severity. PLoS One. 2016;11(12):e0167801.

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