Single Particle Liquid Biopsy Analysis for Acute Myocardial Infarction

Co-supervisor: Prof. Paul Riley, Institute of Developmental and Regenerative Medicine

Commercial partner: SPARTA Biodiscovery Ltd.

Project background and description

Extracellular Vesicles (EVs) are nano-sized membrane vesicles with a phospholipid bilayer and are released by most cells, heathy and diseased, into biological fluids. The lipid, protein and nucleic acid composition of EVs has been found specific to their cell-type origin and therefore it may be possible to trace EVs in biological fluids to their source. Studies by the Riley group have shown that EVs secreted from the epicardium play a critical role in the human heart’s regenerative capacity in response to cardiac injury (Villa del Campo et al. 2021 Cardiovasc. Res.). Therefore, if we are able to characterise the contents of EVs in biological fluids, link them back to their cellular origin (e.g. injured heart tissue) and identify their specific regenerative potential, using EVs as biomarkers can offer a unique, non-invasive liquid-biopsy-based solution for diagnosis and longitudinal monitoring of tissue regeneration including treatment response.
Prof Molly Stevens’ group has developed a novel platform called SPARTA® (Single Particle Automated Raman Trapping Analysis), which is now being commercialised by spin-out company SPARTA Biodiscovery Ltd. This technique offers a unique solution for analyses of EVs by utilizing automated single particle trapping with Raman spectroscopy.  This means SPARTA® can provide high-throughput biochemical information, in the form of Raman spectral fingerprints of individual EVs, enabling us to distinguish between EV subtypes within mixtures, which would not be possible with bulk techniques. Research in the Stevens group (Penders et al. 2021 ACS Nano) has indicated a tremendous potential for sensitive and specific detection of disease vs. healthy cell derived EVs using SPARTA®. 
Under the co-supervision of Prof Molly Stevens and Prof Paul Riley and in close collaboration with industry partner SPARTA Biodiscovery, the goal of this PhD project is to profile EVs from in vitro disease models and patient samples using SPARTA and complementary techniques such as RNA sequencing, to uncover diagnostic and prognostic EV biomarkers of heart disease. The study will serve to validate SPARTA® as a powerful new minimally invasive diagnostic technique of heart disease, as well as a modality for longitudinal monitoring of treatment efficacy and/or tissue regeneration.

Aims

1. Analyse cell-derived EVs using SPARTA® and existing RNA and protein analysis techniques for identifying key EV profiles involved in the different stages of cardiac disease and tissue regeneration.
2. Test these identified EV profiles in human cell-based models to elucidate their functional roles in heart tissue regeneration.
3. Using the EV-profile library, build and validate models for the identification and analyses of disease and tissue regeneration-linked EV biomarkers in patient sample blood plasma-derived EV samples.

Training Outcomes

This multidisciplinary project will combine skills and techniques in in vitro research using cell-based approaches combined with handling, purification and analysis of patient samples, as well as analytical skills in particular around spectroscopy being the core of the SPARTA® technology. In addition, the rich spectroscopic data sets acquired will allow the student to develop key skills in multivariate statistic data analysis, large data modelling and with scope to expand into machine learning techniques for predictive analysis. The project will also encompass applying other complementary EV analyses techniques such as RNA sequencing and flow cytometry. Taken together, the project will provide an enriching interdisciplinary training programme aligned with the priority strategic topics of precision healthcare, diagnostics and digital technologies.

Apply using course: DPhil in Physiology, Anatomy and Genetics