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- Primary supervisor: Dr Kevin Litchfield
- Secondary supervisor: Dr Nicholas McGranahan
This is a 4-year PhD studentship funded by the Rosetrees Trust, which covers tuition fees at Home/EU rate and a stipend of £21,000 per year
Applications are now CLOSED (Monday 18 May 2020)
Project description.
Immunotherapeutics have led to breakthrough improvements in cancer survival, with immune checkpoint inhibitor (CPI) treatments now approved for over a dozen different tumour types. However, typically only 20-40% of patients benefit from immunotherapy, and novel immune targets are urgently needed to expand the proportion of patients who respond to treatment. An effective anti-tumour immune response is underpinned by multiple factors, including the presence of immunogenic HLA-presented peptides, a functional immune cell infiltration into the tumour core, as well ongoing T-cell priming in tertiary or secondary structures. These processes are regulated by a network of costimulatory molecules, as well as influenced by tumour cell intrinsic events, and hence a systems level understanding of immunotherapy response is critically needed.
Experimentally, there are a lack of model systems able to recapitulate the complexity of immunotherapy response, and instead discovery work is now focused on patient samples from clinical trials. Multi-omic profiling of clinical samples has already enhanced our understanding of immunotherapy activity, establishing for example tumour mutation burden as a key driver of CPI response and hence validating the neoantigen hypothesis. It is now tractable to conduct large-scale integrated analysis of multi-omic datasets, generated directly from patient tumour tissue, in order to identify of the next generation of cancer immunotherapy targets. Work over the last five years by the project supervisors has enabled the world’s largest exome/RNAseq dataset from immunotherapy treated patients to be collated. This work is now formalised through an international consortium called Project METIOR (METa-analysis of Immune-Oncology Response), and the PhD project will play a central role in leading this work going forwards. In total genomic/transcriptomic data is already available from n=1500 patients, across eight tumour types, and this is set to increase to n=~5000 patients across the duration of the studentship. As well as bulk tumour exome and RNA sequencing data, Project METIOR will also encompass single cell RNA-seq data, as well HLA-peptidomics data generated using mass spectrometry.
Project objectives
- To undertake a comprehensive training in bioinformatics, spanning pipeline execution, novel methods development, biostatistics and discovery analysis. In terms of techniques, the candidate will obtain direct experience in analysis of whole exome/genome sequencing, RNA sequencing, single cell and proteomics data, as well as scientific expertise in the field of cancer immunotherapy.
- To conduct discovery analysis utilising the Project METIOR dataset, including the identification of novel TCR signalling inhibitory molecules, new sources of tumour specific antigen (e.g. hERVs), and characterisation of mechanisms of tumour cell intrinsic immune escape.
- To contribute to the implementation of predictive immunotherapy biomarkers into prospective clinical trials, in order to support accurate stratification of patients for immunotherapy treatment.
This analysis will build on a strong track record of high impact discoveries in immunogenomics at UCL/Crick Institute, and the candidate will benefit from training in an exciting and dynamic environment. Furthermore, project findings will be validated within the broader context of the TRACERx clinical trial, with extensive clinical biospecimens and datasets available for follow on experiments. Informal enquiries should be directed to k.litchfield@ucl.ac.uk
- Person specification
Essential
· Minimum upper second class Honours Degree in an associated discipline, or an overseas qualification of an equivalent standard.
· Knowledge of tumour biology and immunology, and ideally cancer evolution.
· Preliminary knowledge of research techniques.
· Evidence of motivation for and understanding of the proposed area of study.
· Ability to develop understanding of complex problems and apply in-depth knowledge to address them.
· Potential to develop expertise in new areas of the subject.
· Potential for innovation and initiative, and evidence of an ability to work independently.
· Effective communication skills in both written and spoken English.
Desirable
· Relevant laboratory research experience.
· Experience of R, Python and HPC cluster usage.
Students will also need to qualify as UK/EU fee payers and meet UCL general admissions criteria.
- Duties and responsibilities
Research· To apply highly specialist scientific skills and expertise to lead in the delivery of high quality research and the preparation of high-impact research publications.
· To keep abreast of current developments in this research area.
· To report research progress to the supervisory team, the Cancer Institute, and at scientific conferences and meetings.
· To work with other Scientists within the team as necessary.
· To work safely by adhering to all University policies and practices, including preparing and following laboratory risk assessments, and complying with Health and Safety policies, ethical approval processes and Human Tissue Act guidelines.
Analytical and Judgement Skills
· To demonstrate a high-level of technical and analytical skill to resolve highly complex scenarios, requiring analysis, interpretation and expert judgement to find the most appropriate solutions.
· To identify, interpret and integrate information from a wide variety of sources, and critically evaluate the quality and assumptions of these data.
· To show initiative and the ability to make decisions in areas where no previous work has been undertaken.
· To show awareness of your own developmental needs and undertake appropriate training where appropriate.
· To comply with professional codes of conduct.
- Research environment
The UCL Cancer Institute is a state-of-the-art institute to consolidate cancer research at UCL and promote links with our partner teaching hospitals, in order to support excellence in basic and translational studies. The Institute draws together talented scientists who are working together to translate research discoveries into developing kinder, more effective therapies for cancer patients. It is a Cancer Research UK and Experimental Cancer Medicine Centre, and contains approximately 580 staff, including 120 PhD and MD (Res) students and 40 MSc students. Core facilities within the Institute include: Genomics Facility (gene expression microarrays); Proteomics Facility; Imaging and Cell Sorting (confocal, time-lapsed microscopy, MoFlo FACS); Pathology Suite (laser capture microdissection, tissue arrays); Experimental Imaging (with UCL Institute of Child Health); and Transgenesis.
Funding and application
Applications are now CLOSED
Funding will be for 4 years, with a tax free stipend of £21,000 per year plus UK/EU-level university fees. Due to funding body restrictions, students will need to qualify as UK/EU fee payers.
