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Tissue Cross-Talk in Health and Disease Laboratory

Based at the University of Birmingham, we are interested in complex molecules and extracellular vesicles secreted into circulation in physiological and pathological contexts

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Opportunity to join us!

Our international research support have made us aware of a great funding scheme run by the Huttunen Foundation for prospective Finnish PhD and Postdoctoral Researchers to carry out work in the UK. Ever open to diversifying our team (and science), we’d like to encourage applications to join us via http://www.oskhuttusensaatio.net/apuraha.html . Please check this link for eligibility criteria before contacting us.

What can we offer? Or current body of work centres on Extracellular vesicles (EVs), significant mediators of inter-tissue communication by proteins, miRNAs, lipid and metabolites in pathological contexts such as cancer, metabolic and neurological disease, but also in physiological contexts such as exercise. The latter is a particularly interesting finding as it adds to the concept that some of the positive effects of exercise on health can be explained by a complex network of signalling by proteins within or independently of EVs. While these findings implicate EV trafficking as a fundamental biological process, little is known regarding what signals mediate the delivery, or tropism of EVs to specific sites, or indeed what the exact biological role of this process constitutes. These questions are especially relevant, not only to provide an integrated understanding of health, but also alongside the recognition that EVs show much potential as carriers of therapeutic agents, given that they protect their cargo from degradation and clearance in plasma. Understanding tissue specific tropism of EVs could well be a considerable step in the development of a drug delivery system that avoids entirely the unwanted off-target effects of systemic drug administration.

We are executing a research plan in the coming years that will utilise a range of biological techniques to address these critical research questions. Specifically, the laboratory has developed a ‘pulse chase’ technique whereby tissue specific EV localisation can be tracked using stable isotope labelling of mice. Mice are fed with a chow containing stable isotope lysine and exposed to a physiological stimulus such as exercise, that causes a transient release of EVs into circulation. EVs are then isolated and transfused into unlabelled recipient mice. When analysing recipient tissues via mass spectrometry, owing to their heavier mass, proteins derived from the labelled donor (in EVs) can be distinguished from proteins endogenous to the unlabelled recipient, providing an elegant model to determine (a) which tissues EVs are delivered to (b) which proteins are delivered and (c) which of the known adhesion proteins are especially enriched, implying their role in mediating tropism to that particular tissue.

This approach is especially powerful, when combined with targeted analyses of circulating EVs via modern platforms offering immunoaffinity based colocalization of specific EV subtypes and fluorescence/nanoparticle tracking analysis (Exoview). Once specific proteins are identified that mediate tropism to certain tissues, antibodies against these proteins can be used via the Exoview system to specifically isolate these EVs and phenotype their cargo in humans. Further, since the platform allows colocalization of EV markers and independent fluorescence analysis, this approach facilitates additional information regarding the subtype of EVs that may be carrying specific EV cargo and the potential tissue source, inferred from colocalised surface markers.

The objectives of this research plan are therefore to:-

1)    Examine tissue specific uptake of EVs following exercise

2)    Validate the protein signature in EVs that mediate tissue specific tropism

3)    Identify/validate protein cargo to infer a biological role of this EV delivery in humans.

4)    Identify a tissue source of these EVs

Interested? Please get in touch to discuss at m.whitham@bham.ac.uk. Following an informal interview process, we can help you with your application to the Huttunen Foundation (http://www.oskhuttusensaatio.net/apuraha.html). But HURRY! The deadline is 15th June 2021

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