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Extracellular Vesicles – defining the functional surface proteome of vesicles


School of Biosciences

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Prof A Devitt , Dr D Aubert , Dr A Goddard No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Extracellular Vesicles (EV) are an exciting and novel mode of intercellular communication and they are known to have profound effects on recipient cells. There has been significant work to catalogue the components (e.g. protein, nucleic acid and to lipid components), though remarkably little is known of the functional importance and location of these components.

Research in our laboratories has focused for a number of years on the study of vesicles from dying cells. As cells die in vivo they are removed by healthy ‘undertaker’ cells (phagocytes e.g. macrophages) in a process that resolves inflammation and prevents disease. This is essential to homeostasis and healthy ageing. For clearance of dying (apoptotic) cells to be efficient and timely, dying cells release extracellular vesicles (EV) to attract phagocytes to sites of cell death. Crucially, this interaction of EV with the immune system underpins the control of inflammation, a process central to health, regenerative medicine and many important diseases. Whilst these EV are known to be of greatly varying size (<50nm to >1µm) and derived from different compartments of the dying cell, remarkably little is known of the composition of the EV surface (which will be crucial to the interaction of EV with recipient cells) and how this links to function.

Over recent years, our BBSRC-funded work has yielded extensive detail of the EV proteome but it has proved technically challenging to assess the surface proteome of EV and link this to function across the diverse range of EV sizes. To address this clear gap in our knowledge, this project combines the expertise of Aston (cell death, EV purification and analysis, membrane and macrophage biology) with our company partner NanoFCM (high resolution, multiparameter particle analysis) – two partners with great experience in the exciting field of EV.

Working from our extensive existing data, this project will define the surface proteome of extracellular vesicles across the entire size range of EV generated from dying cells. This novel approach will then help define those factors that are essential for EV functioning in the control of inflammation. EV surface proteome will be linked with function as we address the following key questions. What are the key components of EV that enable communication with the immune system? Do EV of differing sizes and sources interact in a similar manner with the immune system? Is it possible to produce a synthetic EV with a defined surface proteome to act as a mimic of EV function?

The project will use a broad range of techniques to answer these questions including cell culture, particle isolation and analysis, flow cytometry, imaging (light and electron microscopy), assays of immune cell function and inflammation.

Within this project, the successful candidate will work closely with the teams at both Aston University (Birmingham) and Nano-FCM (Nottingham) to realise the impact from this project. The output from this project will be essential to a better understanding of EV fundamental biology that will be of interest to basic scientists and the application of the findings will enable novel approaches to the control of inflammation, of interest to clinicians, pharma and biotech companies. Crucially, this project will help to drive NanoFCM’s development of analyses of small particles (40/50nm and above) with high sensitivity through Nano flow cytometry.

Funding Notes

Studentship includes: fees, a tax free stipend of at least £15,009 p.a (to rise in line with UKRI recommendation); a travel allowance in year 1; a travel / conference budget; a generous consumables budget and use of a MacBook Pro for the duration of the programme.

References

Grant, L., Milic, I. & Devitt, A. (2019). Apoptotic cell derived extracellular vesicles: structure-function relationships. Biochemical Society Transactions: 47(2): 509-516.
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