Exploring the effects of nutrient deprivation on T cells and oncolytic adenoviruses, in order to create immune activators for tumour therapy

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Oncolytic viruses can replicate selectively within the tumour microenvironment and kill tumour cells, before spreading to infect adjacent cells. They can kill cells directly and can also encode potent biologicals for selective expression within tumours. However, viruses must be able to produce multiple copies of themselves under the challenging nutrient-restricted and acidic environment of solid tumours. This project will explore the interface between adenovirus activity and the limitation of amino acid supply within tumours, for example mediated by over-expression of the enzyme IDO which breaks down local tryptophan. It will also cover adenovirus activity under acidic conditions found to be in solid tumours. The work should go on to then monitor the resulting environment following virus infection and how this may affect long term changes in the tumour, for example the activity of immune cells, specifically T cells following oncolytic viral infection. The project will be at the interface of basic biology and therapeutic development and will make use of many techniques including molecular cloning as well as virology and cell culture techniques.