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Development of advanced in vitro models for Dupuytren’s disease

  • Project No: NDORMS-2025/04
  • Intake: 2025

Project overview

Fibrotic diseases affect multiple organ systems, increasing global morbidity and mortality1. Fibrosis is a final common pathway for a wide range of diseases affecting musculoskeletal tissues. Dupuytren’s disease is a common and disabling fibrotic disorder affecting the hand leading to permanent flexural deformities of the fingers2. Current treatments are restricted to surgical division or resection of diseased tissue to improve hand function. Effective treatments to prevent fibrosis and permanent contracture of the fingers are not currently available.

In the absence of animal models that accurately reflect this uniquely human disease, this project will develop a new 3D organoid model3 comprised of patient-derived cells to study Dupuytren’s disease. There are over 50 described GWAS loci for Dupuytren’s Disease4. The 3D model generated in this project will be used to: 1) characterise one or more of these genetic loci, 2) advance understanding of the cellular basis underpinning development of permanent fibrosis, 3) test new therapeutics to prevent permanent fibrosis and finger contracture. 

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 scRNAseq, histology, multiplex immunohistochemistry, flow cytometry, tissue culture utilising 2D & 3D models and nanoindentation.

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 & Furniss Laboratory Group meetings 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 Buckley & Coles collaborating Research Groups:

https://www.ndorms.ox.ac.uk/research/research-groups/stromal-cell-biology

https://www.ndorms.ox.ac.uk/research/research-groups/stromal-and-systems-immunology-group

 

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 and run by the IT department (information will be provided once accepted to the programme).

How to Apply

The Department accepts applications throughout the year but it is recommended that, in the first instance, you contact the relevant supervisor(s) or the Graduate Studies Office (graduate.studies@ndorms.ox.ac.uk) who will be able to advise you of the essential requirements.

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 will commence in October 2025.

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

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

OR

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

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

References 

1.         Thannickal, V.J., Zhou, Y., Gaggar, A. & Duncan, S.R. Fibrosis: ultimate and proximate causes. J Clin Invest 124, 4673-4677 (2014).

2.         Layton, T.B., et al. Cellular census of human fibrosis defines functionally distinct stromal cell types and states. Nature communications 11, 2768 (2020).

3.         Johnson, P.A., et al. Three-dimensional, in-vitro approaches for modelling soft-tissue joint diseases. Lancet Rheumatol 5, e553-e563 (2023).

4.         Riesmeijer, S.A., et al. A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren's disease. Nature communications 15, 199 (2024).

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347226/pdf/JCI74368.pdf
  2. https://www.nature.com/articles/s41467-020-16264-y
  3. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00190-X/fulltext
  4. https://www.nature.com/articles/s41467-023-44451-0

 

The Botnar Institute is a proud supporter of the Academic Futures scholarship programme, designed to address under-representation and help improve equality, diversity and inclusion in our graduate student body. The Botnar and the wider University rely on bringing the very best minds from across the world together, whatever their race, gender, religion or background to create new ideas, insights and innovations to change the world for the better. Up to 50 full awards are available across the three programme streams, and you can find further information on each stream on their individual tabs (Academic futures | Graduate access | University of Oxford).