A multi-omic approach to identifying biomarkers of tissue development

Tissue development, adaptation and degeneration has a profound effect on the health of an individual. This adaptability of biological tissues is associated with the release of specialised growth factors which is partly modulated through cell-derived nanoparticles termed 'extracellular vesicles' (EVs). EVs contain numerous growth factors and RNA molecules implicated in the modulation of transcriptional events. These complex particles also contain a complex arrangement of lipids, which are likely to have influential but as yet undefined contributions to cell fusion events critical for tissue cell formation and regeneration. However, current understanding of the contribution of EVs during tissue adaptation, ageing and degeneration remains limited. This is principally due to (1) a lack of efficient methodologies for the isolation/purification of EVs and (2) a limited understanding of their structural biochemical composition and how this relates to tissue development.

Within this project, we aim to drive advances in EV research to accelerate the development of new healthcare technologies by:

Building on our previous work on EV isolation and analysis to optimise a highly specific EV isolation protocol that will enhance the rate and specificity of EV recovery while eliminating the presence of contaminating biological particulates. The protocol will be applied for the isolation of EVs derived from cell culture experiments to ensure that biomarkers identified in the analytical phase of the project are specific to EVs. This will ensure that outcomes generated in the study have translational value in the healthcare technologies sector.

Applying state-of-the-art analytical techniques to elucidate the protein, lipid and metabolite content of pure EVs isolated from cell culture experiments. These analyses will be carried out in collaboration with the project partner, Waters. We will utilise a multi-omics approach that exploits modern advances in chromatography and mass spectrometry to perform pioneering discovery-based proteomics, lipidomics and metabolomics investigations into EV composition.

By mapping the content and function of EVs during tissue development and adaptation we provide an elegant way of identifying biomarkers that can be applied for the prediction and monitoring of cellular adaptation/degeneration to deliver a rapid and non-invasive biomarker of tissue status. Furthermore, a deeper understanding of biophysical and biochemical changes in EV content in health and disease will allow us to develop strategies for the exploitation of EVs in tissue engineering These two facets will provide a foundation to develop both predictive and curative healthcare technologies.