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Kennedy Trust Prize Studentships

Project Overview

Ankylosing Spondylitis is a chronic inflammatory rheumatic disease affecting young people. 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 now established in our groups. The student will learn immunological techniques to study patient-derived samples and to test this hypothesis, specifically asking:

  1. Are specific gut bacteria associated with AS? 
  2. Are AS patient Th17 responses are driven by organisms from the microbiome, using both clinical isolates and synthetic peptides based upon identified triggering organisms. 
  3. Does microbiome (change) predict flare and/or response to therapy with either anti-TNF or with anti-type 17 biologic therapy such as anti-p19 antagonism? 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.

Training 

The Botnar Research Centre plays host to the University of Oxford's Institute of Musculoskeletal Sciences, which enables and encourages research and education into the causes of musculoskeletal disease and their treatment. Training will be provided in techniques including FACS and FACS analysis, cell culture, immunoassays, bacterial culture and metagenome analysis.

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.

Students will be expected to present data regularly to the department, the Bowness lab meeting at the Botnar and also the Powrie lab at KIR, and to attend external conferences to present their research globally.

Students will also have the opportunity to work closely with the groups of Thibault Griseri (murine modles), and Luke Joskins (statistical genetics).

Relevant Publications

  1. 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 
  2. Rysnik O, McHugh K, van Duivenvoorde L, van Tok M, Guggino G, Taurog J, Kollnberger S, Ciccia F, Baeten D, Bowness P. Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue. J Autoimmun. 2016 Jun;70:12-21. doi: 10.1016/j.jaut.2016.03.009. Epub 2016 Mar 29. 
  3. Jethwa H, Bowness P. The IL23/IL17 axis in Ankylosing Spondylitis: New advances and potentials for treatment. Clin Exp Immunol. 2015 Jun 17. doi: 10.1111/cei.12670. [Epub ahead of print] PMID: 26080615

Scientific Themes

Immunology; Musculoskeletal Science.

Further information

Professor Paul Bowness, NDORMS
paul.bowness@ndorms.ox.ac.uk 

Project reference number #201713

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