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Findlay Bewicke-Copley is from Sherbourne in Gloucestershire. He joined Oxford Brookes as a research student in April 2014 and his thesis title is ‘The role of stress derived extracellular vesicles on the Bystander Effect’.
I had recently moved nearby and attended an open day originally looking to do an undergraduate degree here. Whilst I went elsewhere for my undergraduate degree, Brookes was one of the first places I looked at for my MSc by Research.
I had previously completed an MSc in my current lab and I was interested in continuing with the group.
Between my undergraduate degree and postgraduate career I was working at the O2 Academy on Cowley Road.
I work on Extracellular Vesicles released during stress. Extracellular vesicles are vesicles found within the extracellular space. They have numerous different functions in both healthy and stressed cells, often in intercellular communication. There are three main recognised classes of extracellular vesicle: Apoptotic bodies, microvesicles and exosomes. Apoptotic bodies are formed when cells undergo apoptosis. First there is chromatin condensation followed by membrane blebbing and culminating in the complete degradation of the cell into separate membrane-bound vesicles known as apoptotic bodies (Elmore 2007). Microvesicles are plasma membrane fragments, formed by outward budding of the plasma membrane. They are commonly larger than exosomes, with a range of about 50-2000nm. Whist Exosomes and Microvesicles have often been differentiated by size, it's important to note that it is actually their origin that defines them. Vesicle budding is initiated by the translocation of phosphotidylserine to the outer-membrane and completed by the contraction of the cytoskeleton. Exosomes are very small vesicles of endosomal origin. Whilst they were at one time characterised as being 30-100nm there have been studies suggesting that they can be larger than this, and that other vesicles can, in fact, fall within this spectrum, suggesting size is not a sufficient way to characterise a vesicle population. They also were thought to have a cup shaped morphology, but this was found to be an artefact of fixation for Electron Microscopy. They start as invaginations into late endosomal bodies that bud off into the interior of the endosome, these are then known as multi-vesicular bodies (MVBs). The MVB can then either move to the lysosome and undergo degradation, or move to the plasma membrane. If the latter route occurs the MVB then binds to the plasma membrane and releases its vesicle cargo into the extracellular space.
The main function of EVs that I work on is a thing called the bystander effect. The classical model of stress is that only the cells directly affect by the stress exhibit a stress response, with the surrounding cells and tissues being unaffected. However, there is mounting evidence of non-targeted effects of stress in the form of the bystander effect. The bystander effect is, in brief, the raising of a stress response in cells that have not been exposed to stress. This effect has been observed in many different cell types and organisms.
The first example of the bystander effect was reported in 1992, when cells were treated with α-particles 30% showed sister chromatid exchange, but only 1% were hit by the α-particles. Additional evidence of off-target effects of radiation was observed in 1994 in rat lung epithelium. More cells were found to have increased levels of p53 following α-particles treatment than were estimated to have been directly hit by the particles. Further work on the off target effects of α-particles suggested that some extranuclear target of radiation that could explain the difference between cells traversed by α-particles and damaged cells. As these experiments were often carried out in cells grown in monolayers it believed that gap junction signalling was the mechanism by which bystander cells received these signals. Studies that inhibited gap junction signalling was able to reduce the levels of bystander damage, suggesting that a bystander signal is transferred in this manner. Interestingly this effect is still observed when the whole population is irradiated, the media is harvested and fresh cells are grown in it. As these cells are not in direct contact this data suggests that there is some extra cellular signal that is released by cells into the media. It has been shown that bystander cells treated with extracellular vesicles (EVs) extracted from irradiated cells show a higher level of DNA damage, apoptosis and chromosomal aberration than control cells. Most of my work related to vesicles released following heat shock that induce the bystander effect.
I enjoy being at the forefront of my field and being able to go to conferences and talk with people from all over the world about our work.
There is a large amount of training available that is suited to most fields of research. A lot of the courses are key to effective work and data management.