Kennedy Trust Prize Studentships
Investigating the pathogenesis of inflammatory arthritis with computational and single-cell genomics
Ankylosing spondylitis (AS) is a common and highly heritable1 form of arthritis which characteristically involves inflammation of the sacroiliac joints and spine. Currently, the establishment of chronic inflammation in AS is thought to involve the IL-23/IL-17 immune pathway2, various immune cell types (such as Th17 cells, neutrophils, innate lymphoid cells and macrophages) as well as dysbiosis of the gut microbiome. Historically, however, the extraordinary heterogeneity of the immune system has posed a major roadblock to the identification of the context-specific factors responsible for initiating and sustaining inappropriate inflammatory responses in diseases such as AS. To address this, we are now using cutting-edge ultra-high-throughput single-cell RNA-sequencing technologies to directly survey the immune system and inflamed joints of AS patients.
In this mainly computational project, you will learn and develop new single-cell genomics3 analysis methods in order to discover cell types, cell states, biological pathways and genes associated with the development of AS. Working closely with experimental colleagues you will design follow-up experiments and test hypotheses using the latest functional genomics approaches such as CRISPR-based gene editing. Ultimately, the results of this research are expected to inform and accelerate the development of much-needed selective therapeutics for this debilitating condition.
The Kennedy Institute is a world-renowned research centre, housed in a brand new, state-of-the-art facility at the University of Oxford. Students will become fluent in computational genomics and acquire an expert understanding of chronic inflammatory disease. Training will be provided in techniques including the writing of computational pipelines with Python, the use of Linux high-performance compute clusters, and statistical data analysis and visualisation with R. Students will have the opportunity to utilise machine learning approaches, to work closely with world-leading statistical geneticists, and will perform integrated analyses with “big data” from sources such as the Human Cell Atlas and ImmGen projects. You will be expected to develop a close understanding of experimental research - for example by regular attendance of wet-lab group meetings - and will have the opportunity to be closely involved in the generation of functional genomics data.
A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology and data analysis. Students will attend weekly seminars within the department and those relevant in the wider University. You will be expected to present data regularly to the department, the Sansom and Bowness groups and to attend external conferences to present your research to an international audience.
- HLA-B27. Bowness P. Annual Review Immunology, 2015
- The interleukin (IL)-23/IL-17 axis in ankylosing spondylitis: new advances and potentials for treatment. Jethwa H, Bowness P. Clin Exp Immunology, 2016
- Population and single cell genomics reveal the Aire-dependency, relief from Polycomb silencing and distribution of self-antigen expression in thymic epithelia. Stephen N. Sansom, Noriko Shikama-Dorn, Saule Zhanybekova2, Gretel Nusspaumer, Iain C. Macaulay, Mary E. Deadman, Andreas Heger, Chris P. Ponting, Georg A. Holländer. Genome Research, 2014
Bioinformatics, Statistics and Computational Biology; Genes, Genetics, Epigenetics and Genomics; Immunology; Musculoskeletal Science; Translational Medicine and Medical Technology
How to Apply
The department accepts applications throughout the year but it is recommended that, in the first instance, you contact the relevant supervisor(s) or the Directors of Graduate Studies who will be able to advise you of the essential requirements.
Interested applicants should have or expect to obtain a first or upper second class BSc degree or equivalent, and will also need to provide evidence of English language competence. The University requires candidates to formally apply online and for their referees to submit online references via the online application system.
The application guide and form is found online and the DPhil or MSc by research will commence in October 2017.
When completing the online application, please read the University Guide.