Our research group combines leading experts in inflammatory arthritis and ocular immunology. We study human disease and use experimental animal models and cutting-edge methodologies to gain insight into fundamental biological mechanisms that promote tissue pathology. We are offering an exciting 3-year PhD studentship jointly funded by Fight for Sight and Versus Arthritis. The successful candidate will explore immunological mechanisms that link systemic immune dysregulation with co-existing joint and ocular inflammation.
A well-established association exists between sight-threatening uveitis and inflammatory arthritis. Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis and Behçet’s syndrome are all associated with co-existing ocular and joint inflammation. These diseases commonly feature an aberrant systemic CD4 T-cell response and local immune cell activation that drives pathology. Despite this, uveitis and arthritis are typically studied in isolation which has hampered the discovery of disease and immune interactions that promote uveitis-associated arthritis.
Clinical onset of arthritis typically precedes ocular involvement. Thus, a change in the ocular immune microenvironment as a consequence of arthritis may mark early disease. Our studies reveal that the induction of arthritis promotes an accumulation of leukocytes within the eye that is indistinguishable from pre-clinical uveitis. We have also identified cytokine-regulated mechanisms that limit ocular and joint pathology. Based on these studies, the student will address the hypothesis that cytokines acting as important immune checkpoints are dysregulated in inflammatory arthritis, which results in coincident ocular and joint damage mediated by T-cell and neutrophil crosstalk.
To address this hypothesis, the student will receive training in animal models of arthritis and uveitis, clinical imaging, flow cytometry and cutting-edge next-generation sequencing methods (e.g., RNA-sequencing). These techniques will be used to define temporal changes in the ocular microenvironment upon arthritis induction and to identify shared transcriptional signatures that reflect immune effector functions active across the eye and joint. Finally, the project will determine whether interventions that inhibit cellular infiltration or effector functions prevents co-existing arthritis and uveitis to restore tissue homeostasis.
The student will join flourishing arthritis and ocular immunology research groups based in the Biomedical Sciences Building at the University of Bristol. Our institution is a top-ranked research-intensive University with state-of-the-art research facilities. At the School of Cellular and Molecular Medicine, our newly refurbished laboratories are well-equipped and have access to excellent core-funded flow cytometry, microscopy/imaging, genomics and proteomics facilities. Research excellence in this area is recognised through investment from the NIHR Biomedical Research Centre for Ophthalmology, which supports a partnership with University College London's Institute of Ophthalmology and the Moorfields Eye Hospital. Here, Bristol is the Centre's lead on inflammation and immunotherapeutics.
The candidate will start in October 2021 although there may be some flexibility with the start date. They will be directly supervised by a team consisting of Dr Gareth Jones and Dr Lindsay Nicholson, with additional support from Dr Borko Amulic and Dr Barbara Szomolay (Systems Immunity Research Institute, School of Medicine, Cardiff University).
Candidate requirements:
Applications are sought from high performing individuals who have a 1st or 2.1 higher degree (or equivalent) in a biomedical or related life sciences discipline. Possession of a relevant Master’s degree or research experience would be advantageous but is not expected.
Funding:
The studentship is jointly funded by Fight for Sight and Versus Arthritis and includes a stipend of £17,000 per year and a research consumables allowance. Tuition fees are included at the rate of UK students. International applicants may apply if they can fund the difference in fees between overseas and UK rates (currently £19,425 per year). The studentship also includes a research consumables allowance. Standard University of Bristol eligibility criteria apply.
How to apply:
Please make an online application for this project at http://www.bris.ac.uk/pg-howtoapply. Please select the Faculty of Life Sciences and Cellular and Molecular Medicine (CMM) PhD programme from the lists presented. You will be prompted to enter details of the studentship in the Funding and Research Details sections of the form.
For general enquiries linked to the online application process, please email [Email Address Removed]
Further information:
For informal enquiries or further information about this PhD project, please contact Dr Gareth Jones ([Email Address Removed]). Visits are welcome but not essential and will be organised in the light of government and university guidance at the time.
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