Exploring the biological relevance of extracellular vesicle trafficking in health and disease

Secondary Supervisor(s): Dr Paul Harrison

University of Registration: University of Birmingham

BBSRC Research Themes: Integrated Understanding of Health (Ageing, Diet and Health)

Project Outline

In both disease and healthy states, cells of the human body release molecules such as proteins, lipids and RNAs into circulation within nano-sized particles called extracellular vesicles (EVs). While it may be intuitive that this process might inform the disease process, or physiological adaptation, the biological relevance of EV release, and subsequent uptake in distal cells is poorly understood.

Our research group examines the fundamental concept that in response to both physiological and pathological stimuli, the transfer of molecules from one tissue to another via EVs is a biologically meaningful event and importantly, that broad assessment of the molecular cargo can be insightful.

By way of an example, we have previously used cutting-edge, quantitative proteomic techniques to identify a significant and vast proteome released into circulation in EVs with a single exercise bout. Such is the observed complexity of this proteome, it is intriguing to explore the possibility that much of this transported information might play a role in mediating some of the known benefits of exercise and whether this information can be exploited for therapeutic benefit. Inherent in this pursuit is a programme of well-designed experiments that seek to understand the tissue source, destination and uptake mechanisms of circulating EVs and indeed, the functional impact of molecules ‘delivered’ from one tissue to another as a consequence of exercise. Furthermore, owing to the observation of a large number of metabolic enzymes circulating in EVs during exercise, we have a keen interest in whether nutritive state, in health and disease, alters EV dynamics and the transported molecular cargo.

An expansion of this research theme is the adoption of similar methodological approaches to examine circulating EVs and their cargo in various conditions such as Ageing, Diabetes, Cancer, Neurodegenerative and Heart diseases. The objective here is to not only provide added insight into the aetiology of these conditions, but explore the notion, building on the observation of the vast EV proteome, that a broad “omics’ analysis of the proteins circulating with EVs can be diagnostic or informative of an impending clinical change.

The proposed studentship will sit within this broad programme of research operating within a modern, ‘wet’ laboratory combining innovative, mass spectrometry-based proteomic analyses with a variety of EV isolation and nanoparticle imaging analysis methods. These primary approaches will be supplemented by traditional laboratory techniques such as Western Blot, RT-PCR and Cell culture. Experience of the more technical methods is preferred but not essential.

More information about the lab can be found at our website https://tissuecrosstalklab.wordpress.com/about/

Key references

Whitham, M. et al. Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise. Cell Metabolism 27, 237–251 (2018).

Fuller, O. K., et al. The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles. Cells 9, 2182 (2020).

Hooten, N. N. Extracellular vesicles and extracellular RNA in aging and age-related disease. Translational Medicine of Aging 4, 96–98 (2020).