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Dr David Greening Research Fellow, Biochemistry

Extracellular vesicles are sophisticated signalling mediators, transporting select RNA and protein cargo. As secreted vesicles they have the capacity to enable intercellular communication and have become the focus of exponentially growing interest, both to study their functions and to understand ways to use them in the development of minimally invasive diagnostics. Importantly, extracellular vesicles are released into biological fluids including blood, urine, uterine fluid, and protect their cargo against degradation and denaturation in the extracellular environment.

With various sub-types of secreted vesicles, including exosomes, are comprised of a lipid bilayer containing various proteins, RNAs and bio-active lipids. They act as intercellular messengers that give the ability to communicate between both cells of the same type and other cell types in distant organs. They are released by healthy cells, both constitutively and upon cell activation and play an important role in immune system function. Exosomes are essential for healthy physiological conditions, however under pathological circumstances, they act to potentiate cellular stress and damage. We aim to gain a better understanding on the definitive molecular mechanisms of function of extracellular vesicles, as well as investigating their capacity to target and reprogram the extracellular milieu (or in recipient cell). The advanced-nano approaches developed in our lab have identified novel regulators of secretome and extracellular vesicle biology and have utilised this knowledge for commercial and translational potential.

The Molecular Proteomics laboratory has utilised quantitative high-resolution mass spectrometry (Q Exactive HF-X Orbitrap) to deliver a superior combination of acquisition speed, resolving power, mass accuracy, spectral quality, and sensitivity. Our pipeline is focused on the rapid identification using chemical labelling and isotopic labelling strategies, in addition to label-free quantitation. We focus on utilising this technology to understanding the secreted and extracellular vesicles molecular drivers of intercellular communication and metabolism, and also defining proteome changes and key pathways involved in tissue health during cardiovascular disease.

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