Lead Institute / Faculty: Cancer Sciences Unit, Faculty of Medicine
Main Supervisor: Dr Matthew Rose-Zerilli; [email protected]
Other members of the supervisory team:
Professor Tim Underwood; [email protected]
Professor Tim Elliott BA PhD; [email protected]
Professor Paul Skipp PhD; [email protected]
Professor Jacek Brodzki; [email protected]
Duration of the award: 48 months (4 yrs) full time
Advances in cancer immunotherapy have proven that the immune system can be directed to kill cancer cells. Southampton is leading the UK in cancer immunology research based in the our newly built £25M Centre for Cancer Immunology. Current immune checkpoint inhibitors licenced for clinical use fail many patients with only 10-60% of treated patients reaching objective response rates and this is accompanied by high cost and serious side effects in some patients. It is thought that immunotherapy is not effective in all patients because certain cancer cells can hide or produce signals that stop the immune system from attacking the tumour. The same mechanisms are thought to mitigate against the success of anticancer vaccines. Current research to address the reasons for inter-patient variability in response to immunotherapy has focused on tumour immune phenotypes, somatic mutation, the gut microbiome or host genetics. There is new evidence to suggest that the tumour microenvironment (TME) maybe a determinant of antigen presentation and therefore play an important role in the development of anti-tumour immune responses in cancer. We need innovative research to understand more about the role of the TME in tumour antigen presentation and cancer immunosurveillance.
This PhD will focus on oesophageal cancer as this disease type has high levels neoantigen presentation and we have world-leading expertise in this field (whole genome sequencing, single-cell sequencing, organoid modelling and immunopeptidomics). As yet these data have not been integrated in a coherent manner to answer important clinical questions. Specifically, this PhD will address the hypothesis that, ‘The tumour microenvironment is a determinant of antigen presentation and immune response in oesophageal cancer’. The main aims of this PhD are to: (1) Link the tumour transcriptome to the immunopeptidome by mathematical modelling of neo-antigen peptide loading to MHC-I molecules. (2) Place antigen presentation into the context of tumour (immune) microenvironment.
The PhD student will acquire data analytic skills, where they will use predictive mathematical modelling to determine the likelihood of selection, and expression level of tumour neoepitopes and components of the antigen processing and presentation pathway, using immunopeptidomic and transcriptomic data from primary human tumour samples. The student will then extend these analyses via further bioinformatical approaches (WGNCA, CIBERSORT & topological data analysis;); focussing on cytokine gene expression signatures, leukocyte infiltration and cancer-associated fibroblasts. These are all factors that determine immunological control of cancer. The student will then investigate the impact of TME/ tumour immunophenotype on the diversity of immunopeptidome presentation by using our novel antigen presentation reporter systems in organoid models. This work will validate the mathematical models developed to predict the level and diversity of peptide presentation.
The student will work in the University priority area of Cancer Immunology at the nexus of three Faculty strategic priorities: cross-Faculty multidisciplinary research, patient proximal research with clear translational potential.
Please contact: Dr Matthew Rose-Zerilli; [email protected]
; Tel: +44(0)23 81205163
Person Specification: https://jobs.soton.ac.uk/Upload/vacancies/files/20562/USE%2003%20Doctoral%20Researcher%20Person%20Specification_UoS_FoM_PhD%20Khakoo%20Hunter.docx
The successful candidate is likely to have the following qualifications:
• A 1stor 2:1 degree in a relevant discipline and/or second degree with a related Masters
Administrative contact and how to apply:
Please complete the University’s online application form, which you can find at https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Login?pos=7205&majr=7205&term=201920
You should enter Dr Matthew Rose-Zerilli as your proposed supervisor. To support your application, provide an academic CV (including contact details of two referees), official academic transcripts and a personal statement (outlining your suitability for the studentship, what you hope to achieve from the PhD and your research experience to date). At interview you will be expected to deliver a short presentation (10 mins max) on your background and research experience at the start of the interview.
Informal enquiries relating to the project or candidate suitability should be directed to Dr Matthew Rose-Zerilli ([email protected]
; Tel: +44(0)23 81205163).
Closing date: Sunday 7th April 2019
Interview date: Tuesday 7th May 2019