About the Project
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.
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