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  BioFlare: Identifying the cellular basis of flare in synovial tissue


   Institute of Inflammation and Ageing

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  Prof Andrew Filer, Dr A Pratt, Dr M Kurowska-Stolarska  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Research interests/description of main research theme:

Despite the introduction of novel targeted therapies in Rheumatoid Arthritis (RA), disease flare occurs in approximately 50% of patients, is poorly understood, and negatively impacts quality of life and joint damage. RA is the commonest immune mediated inflammatory disease, and flares contribute significantly to the cost of RA to society, estimated at some £4bn per year. Understanding of the mechanisms in the joint (synovium) underlying flare is only just starting to emerge thanks to well-designed studies within the Versus Arthritis RACE (Research into Inflammatory Arthritis Centre Versus Arthritis) centre of excellence linking Birmingham, Glasgow, Newcastle and Oxford1,2. RACE with its collaborators has recently been responsible for key paradigm-changing publications using single cell technologies to advance understanding of RA pathogenesis2,3,4,5,6. BioFlare is a £3.5m MRC funded RACE multicentre clinical study in which we are using withdrawal of conventional disease modifying therapy from patients in clinical remission as a model of flare versus remission with a 50% flare rate (pilot BioRRA study1). In BioFlare we have collected synovial tissue biopsies from patients at baseline and at flare, providing cross-sectional and longitudinal comparisons.  

The purpose of the project is to analyse these samples in order to understand the cellular basis of flare. You will undertake training in histological analysis of synovial tissue, and receive training by our groups with expertise in cutting edge technologies including 10x Chromium single cell “Total”RNAseq (Cite-Seq) and multiparameter spatial mass cytometry imaging7, integrating clinical, histological, transcriptomic and spatial data in order to identify biomarkers of subsequent flare vs remission after treatment withdrawal, and to analyse longitudinal tissue samples identifying cellular mechanisms that play key roles in the development of flare. 

In order to build further on these datasets, you will be encouraged to exploit opportunities available within the RACE centre including:

1. Cross referencing to existing datasets in Glasgow, Newcastle and Birmingham informed by the NIH AMP Phase I and Phase II datasets

2. Established tissue imaging techniques including fluorescence imaging, RNAScope, and BD Rhapsody disaggregated single cell analysis

3. Tissue organoid studies reconstituting key populations developed in Glasgow and Birmingham

With Bioflare recruitment ongoing, we already have enough tissue samples available to complete this unique project. 

The Research into Inflammatory Arthritis Centre Versus Arthritis (RACE) is a collaboration between the Universities of Birmingham, Glasgow, Newcastle and Oxford, with funding and support from Versus Arthritis. The programme capitalises on the expertise of the contributing academic institutions, and offers an outstanding opportunity for students to undertake excellent project-based research training within world-class research environments.  The current project describes one of a total of 12 PhD studentships available across the collaborating Institutes over the project period; for all currently available studentships please see  http://www.race-gbn.org/phds/racephdstudentships-applications2021/

Person Specification

Applicants should have a strong background in biological science, and ideally a background in informatics. They should have a commitment to research in biomedical science and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a biological or related subject. 

How to apply

Informal enquiries should be directed to Dr Andrew Filer, [Email Address Removed]

To apply, please send: 

• A detailed CV, including your nationality and country of birth;

• Names and addresses of two referees; 

• A covering letter highlighting your research experience/capabilities;

• Copies of your degree certificates with transcripts;

• Evidence of your proficiency in the English language, if applicable.

Biological Sciences (4)

Funding Notes

Support includes an annual stipend at RCUK rates for 4 years, PhD registration fees at UK student rate, research expenses and travel costs.

References

References
1. Baker KF et al. J Autoimmun 2019; 105: 102298
2. Alivernini S et al. Nat Med 2020; 26): 1295-1306.
3. Croft et al. Nature 2019; 570: 246-251.
4. Rao DA et al. Nature 2017; 542: 110-114.
5. Wei K et al Nature 2020; 582: 259-264
6. Zhang F et al Nat Immunol 2019; 20: 928-942
7. Warren et al Sci Reports 2020;10: 15336

Where will I study?