PhD Studentship: The role of the ESCRT in EV production and oral cancer progression

Oral cancer mortality rates have increased by ~10% in the UK in the last decade. According to Cancer Research UK, there were 2386 oral cancer related deaths in 2014. Sixty percent of patients present with late stage oral cancer, after the tumour has spread to produce regional metastases, as many early cancers are asymptomatic. Extracellular vesicles (EVs), including exosomes and microvesicles, are increasingly recognised as a source of biomarkers for disease diagnosis and also as novel therapeutic targets. They are nanoscale sized, membrane enclosed vesicles that contain molecular cargo including nucleic acids and proteins. They are produced by all cells of the body and are present in biological fluids including saliva. Indeed, the saliva of oral cancer patients contains up to 4-fold more EVs than that of healthy volunteers. Cancer cells produce increased numbers of EVs with altered molecular cargo. These EVs can be taken up by cells that surround the tumour, which converts them to a pro-tumourigenic phenotype. A number of key proteins that are involved in the biogenesis of EVs have already been identified, including the components of the endosomal sorting complex required for transport (ESCRT). ESCRT proteins are involved in a range of cellular processes, in addition to vesicle formation, including cytokinesis and repairing nuclear envelope damage. We have data showing that there is widespread ESCRT dysregulation in oral cancer compared to normal cells, suggesting that the above processes may be abnormally regulated in oral cancer.

The current project will use a variety of cell (cell culture, EV isolation), molecular biology (QPCR, western blotting, and transfection) and imaging (immunofluorescence microscopy, transmission electron microscopy) techniques to elucidate the role of the ESCRT in oral cancer progression. The successful student will join the ‘Extracellular vesicle research group’ (http://vesicle-research.group.shef.ac.uk/) under the supervision of Dr Stuart Hunt (https://www.sheffield.ac.uk/dentalschool/people/hunt_s). Please direct enquiries about the project to Dr Hunt (s.hunt@sheffield.ac.uk).

Funding Notes

The Faculty Scholarships for Medicine, Dentistry & Health cover fees and stipend at Home/EU level. Overseas students may apply but will need to fund the fee differential between Home and Overseas rate from another source.