Kennedy Trust Prize Studentships
Is Ankylosing Spondylitis caused by aberrant immunity to intestinal flora?
Ankylosing Spondylitis is a chronic inflammatory rheumatic disease with onset in young adulthood. We hypothesize that AS is triggered by an abnormal immune response to gut bacteria. Recent advances in sequencing technologies enable the high throughput study of bacterial community composition and are established in our groups. The student will learn immunological techniques to study patient-derived samples and to test this hypothesis, specifically asking the following questions: 1) Are specific gut bacteria associated with AS? 2) Are AS patient Th17 responses driven by organisms from the microbiome. They will use both clinical isolates and synthetic peptides based upon identified triggering organisms. 3) Does change in microbiome predict flare and/or response to therapy with either anti-TNF or anti-type 17 biologic (secukinumab) therapy? We will collect sequential stool and blood samples from patients (not initially on biologic therapy), at time of flare and at 3 months following initiation of anti-TNF or anti-IL17 therapy. 4) What is the association between gut microbiome, GI tract inflammation and joint inflammation? Murine models up and running in the Powrie lab will allow transfer of potentially pathogenic bacteria and then tracking of immune responses and induction of arthritis.
NDORMS, comprising both the Botnar Research Centre and the Kennedy Institute, is a world-renowned research centre. Full training will be provided in a range of immunology and molecular biology techniques. There may be opportunities to pursue microbiological and bioinformatic analysis of metagenomics data and also to visit collaborating groups in the USA (see Inflammatory Arthritis Microbiome Consortium).
A core curriculum of 20 lectures will be taken in the first term of year 1 to provide a solid foundation in musculoskeletal sciences, immunology and data analysis. Students will attend two weekly departmental meetings (Bowness lab at Botnar and Powrie lab at KIR) and will be expected to attend seminars within the department and those relevant in the wider University. Subject-specific training will be received through our group's weekly supervision meetings. Students will also attend external scientific conferences where they will be expected to present the research findings.
- de Wit J, Al-Mossawi MH, Hühn MH, Arancibia-Cárcamo CV, Doig K, Kendrick B, Gundle R, Taylor P, Mcclanahan T, Murphy E, Zhang H, Barr K, Miller JR, Hu X, Aicher TD, Morgan RW, Glick GD, Zaller D, Correll C, Powrie F, Bowness P. RORgt inhibitors suppress Th17 responses in inflammatory arthritis and inflammatory bowel disease. J Allergy Clin Immunol. 2016 Mar;137(3):960-3.
- Schiering C, Krausgruber T, Chomka A, …and Powrie F. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature. 2014 Sep 25;513(7519):564-568.
- Jethwa H, Bowness P. The IL23/IL17 axis in Ankylosing Spondylitis: New advances and potentials for treatment. Clin Exp Immunol. 2015 Jun 17.
Immunology, Musculoskeletal Science
Contact: Prof Paul Bowness, NDORMS University of Oxford.