Enhancing immune stimulation of novel anti-cancer viral vaccine vectors

The ‘GW4 BioMed MRC DTP’ is awarding up to 18 studentships with an October 2020 start date, aligned with the themes of Infection, Immunity and Repair; Neuroscience and Mental Health; and Population Health. The DTP also places a strong emphasis on cross-cutting skills priorities (quantitative skills, interdisciplinary skills and in vivo skills), and may advertise projects outside these themes. The DTP welcomes students from non-medical backgrounds and can fund additional training to assist discipline conversion. Most studentships will be 3.5 years full time or up to 7 years part-time, and can be longer where additional training is undertaken.

PROJECT DESCRIPTION

Human cytomegalovirus (HCMV) is a major cause of mortality and morbidity in the immunocompromised, and if it crosses the placenta to an unborn baby - over 1,000 babies are affected every year in the UK. However, the virus also exhibits two unique properties that have made it a paradigm for understanding the ways that pathogens interact with the immune system. Firstly, once caught, HCMV is never killed by the immune system, despite infecting professional antigen presenting cells (APCs) such as dendritic cells and macrophages, which would normally drive an effective anti-viral immune response. Understanding how the virus achieves this impressive feat is revealing important details about the underlying function of the immune system. Secondly, the virus is able to ‘re-target’ the immune system to fight other diseases very efficiently. This makes the virus extremely interesting as a vaccine vector, and we are actively working to use HCMV as a vaccine vector against cancer. However we still do not understand how the virus achieves these twin feats of avoiding being killed, while inducing large immune responses. This proposal will therefore use cutting-edge multiplexed quantitative proteomics to determine how HCMV manipulates APCs, how this affects the ability of the immune system to control infection and how it enables the virus to so efficiently re-target the immune system against other diseases.

The knowledge gained from this work will have implications for our understanding of all pathogen infections, the functioning of the immune system in health and disease, and the generation of novel viral vaccines against multiple diseases, including cancer.

The successful applicant will receive training in an exceptionally broad range of techniques, including molecular biology, virology, functional immunology, tissue culture, and state-of-the-art quantitative proteomics. They will work in a well funded lab, with multiple grants from both the Medical Research Council, and the Wellcome Trust.

Our work is published in world leading journals including Cell, Science and PNAS. To see example of the work and papers from our lab, please visit our webpage: https://www.cardiff.ac.uk/people/view/126743-stanton-richard

ELIGIBILITY

The DTP welcomes students from both biomedical and non-biomedical backgrounds (especially in areas of computing, mathematics and the physical sciences) and can fund additional training, including Masters, to assist discipline conversion. Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK in an appropriate degree subject. Applicants with a Lower Second Class degree will only be considered if they also have a Master’s degree or have significant relevant non-academic experience.