Fibrosis across musculoskeletal tissues: Comparison of resolving and persistent fibrotic niches

Project overview

Injury or disease of adult tissues incites an inflammatory response during healing. Failure to resolve inflammation favours the development of dysregulated immune responses and fibrosis. Fibrosis is the final common pathway for a wide range of diseases affecting musculoskeletal tissues causing pain and disability, e.g., arthrofibrosis. Conversely, frozen shoulder affecting the shoulder joint capsule is a form of arthrofibrosis that is frequently self-limiting. By studying frozen shoulder patient tissues and cells, we identified that distinct populations of tissue resident cells provide a resolving fibrotic niche conducive to restoring homeostasis during frozen shoulder(1).

The precise cellular and molecular cues that determine whether inflammation resolves or persists, driving fibrosis remain to be identified. Knowledge from how fibrosis resolves in the shoulder joint capsule could inform the biological cues to help prevent irreversible fibrosis of other joints. This project will identify pro-resolving circuits active in frozen shoulder where fibrosis is self limiting, investigating how these circuits become dysregulated in musculoskeletal diseases where fibrosis persists. The project will also utilise established tissue culture models as functional assays to identify the cell types and molecules causal to fibrosis and resolution. Findings from this research will identify new therapeutic strategies to help prevent arthrofibrosis, addressing an unmet clinical patient requirement.

Training

The Botnar Institute 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 scRNAseq, histology, multiplex immunohistochemistry and tissue culture utilising 2D & 3D models.

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, data analysis and the microbiome.  Students will also be required to attend regular seminars within the Department and those relevant in the wider University.

Students will be expected to present data regularly in Departmental seminars, the Dakin Soft Tissue Joint Disease Group and to attend external conferences to present their research globally, with limited financial support from the Department. Students will also have the opportunity to work closely with the Furniss Group within NDORMS.

Students will have access to various courses run by the Medical Sciences Division Skills Training Team and other Departments. All students are required to attend a 2-day Statistical and Experimental Design course at NDORMS (information will be provided once accepted to the programme).

How to Apply

Please contact the relevant supervisor(s), to register your interest in the project, and, if required, the departmental Education Team (graduate.studies@ndorms.ox.ac.uk), who will be able to advise you of the essential requirements for the programme and provide further information on how to make an official application.

Interested applicants should have, or expect to obtain, a first or upper second-class BSc degree or equivalent in a relevant subject and will also need to provide evidence of English language competence (where applicable). The application guide and form is found online and the DPhil or MSc by research will commence in October 2026.

Applications should be made to one of the following programmes using the specified course code.

D.Phil in Musculoskeletal Sciences (course code: RD_ML2)

MSc by research in Musculoskeletal Sciences (course code: RM_ML2)

D.Phil in Molecular and Cellular Medicine (course code: RD_MP1)

MSc by research in Molecular and Cellular Medicine (course code: RM_MP1)

For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford.

References

1.         M. T. H. Ng, R. Borst, H. Gacaferi, S. Davidson, J. E. Ackerman, P. A. Johnson, C. C. Machado, I. Reekie, M. Attar, D. Windell, M. Kurowska-Stolarska, L. MacDonald, S. Alivernini, M. Garvilles, K. Jansen, A. Bhalla, A. Lee, J. Charlesworth, R. Chowdhury, P. Klenerman, K. Powell, C. P. Hackstein, I. Consortium, D. Furniss, J. Rees, D. Gilroy, M. Coles, A. J. Carr, S. N. Sansom, C. D. Buckley, S. G. Dakin, A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution. Nature communications 15, 1394 (2024). DOI: 10.1038/s41467-024-45341-9