About the Project
Knee osteoarthritis (OA) is the most common form of arthritis, affecting 5.4 million people in the UK. At advanced stages of disease, OA is characterised by loss of cartilage and inflammation and fibrosis of the synovial tissue that surrounds the joint. However, as patient symptoms including pain and joint stiffness often apprear late in the disease process, it has been difficult to study the onset and progression of the disease in humans.
While research into disease modifying OA drugs has been extensive, treatments are limited. Consequently, surgery is the only option at advanced stages of the disease, meaning approximately 100,000 people undergo partial or total knee replacement surgery for knee OA each year in the UK.
Unresolved pain and continued loss of function underlies revision and failure of total knee replacements, while patients who require revision of partial knee replacements often have progression of OA. This last group of patients presents a unique opportunity to study the progression of OA in a different way. During joint replacement, the cartilage and ends of the bones are removed, but the synovial tissue remains. The synovium is a rich source of pain- and inflammation-mediators and is therefore likely to play a critical role in driving and modifying the response to knee replacement for OA.
This 3-year full-time DPhil post at the Botnar Institute will embed a student within a dynamic and interdisciplinary team. You will use next generation sequencing data, imaging, and in vitro models to understand, model, and modify the progression of OA. You will address a significant unmet clinical need, and deliver critical next-generation reference datasets of diseased synovium to the Human Cell Atlas.
Ultimately this DPhil will identify ways of improving outcomes for patients undergoing knee replacement for OA. You will:
- Write a critical literature review and/or systematic review on current understanding of the biological pathways underlying progression of OA in humans.
- Analyse in-house next generation sequencing data (bulk RNA-seq and single nucleus RNA-seq of synovial tissue) to identify critical cell types and pathways contributing to OA progression from UKR primary surgery to UKR-to-TKR revision surgery. Publicly available transcriptomics data on other OA-affected soft joint tissues can be integrated and interrogated to enrich signatures and identify targetable pathways for treatments. To address patient factors that may influence OA progression, these signatures will be stratified by patient demographics (e.g. sex, BMI) and clinical information (e.g functional scores, radiographic findings).
- Use in vitro/ex-vivo models to test potential interventions for OA progression. This will include culturing primary cells and synovial explants to modify the pathways identified as contributing to OA progression, such as those involved with pain, vessel ingrowth, fibrosis, and hyperplasia.
Supervisors: The supervisor team are Associate Professor Sarah Snelling and Dr Jolet Mimpen. Work will be within the Snelling Soft Tissue Repair Group, that is composed of postdoctoral scientists, clinical fellows, research assistants and DPhil students.
SELECTION CRITERIA
Essential
- A degree in a biomedical, medical or related subject
- Excellent communication skills
- Experience of writing scientific essays, documents, or dissertations
- Experience of working or studying within a research environment
- Willingness to learn laboratory and computational methods
Desirable
- Experience of processing human tissue samples
- Laboratory and/or computational analysis experience of sequencing methods
- Imaging experience
BENEFITS
The Botnar Institute for Musculoskeletal Science – part of Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) - plays host to the University of Oxford's Institute of Musculoskeletal Sciences, which leads research and education into the causes of musculoskeletal diseases and their treatments.
A core curriculum of lectures in the first term will provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation and translational immunology. All students are required to attend a 2-day Statistical and Experimental Design course at NDORMS and participate at regular seminars/workshops within the Department/their research team. Students will have access to various courses run by the Medical Sciences Division Skills Training Team and other Departments.
We will ensure hands-on laboratory and computational training and embedding within the Snelling Group team who have extensive experience in musculoskeletal biology and international cell atlasing projects. This provides laboratory and computational guidance both locally and internationally.
Finally, the student will be expected to regularly present data in Departmental seminars, the Soft Tissue Repair group & multi-team computational meetings. You will work alongside the Arthritis UK Centre for Osteoarthritis Pathogenesis, attending regular meetings with our collaborators at the Kennedy Institute of Rheumatology. Attendance at National and International meetings will also be encouraged, for which financial support is available.
HOW TO APPLY AND APPLICATION REQUIREMENTS
You should contact Professor Sarah Snelling or NDORMS Graduate Studies (graduate.studies@ndorms.ox.ac.uk). 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 2027. Applications should be made to the following programme using the specified course code (for online application):
- D.Phil in Molecular and Cellular Medicine (course code: RD_MP1).
Further information can be found here.
Applications open mid-September
Application deadline: 12:00 on 1st December
References
Sanchez-Lopez, E., Coras, R., Torres, A. et al. Synovial inflammation in osteoarthritis progression. Nat Rev Rheumatol 18, 258–275 (2022). https://doi.org/10.1038/s41584-022-00749-9
Zhang L, Xing R, Huang Z, Ding L, Zhang L, Li M, Li X, Wang P and Mao J (2021) Synovial Fibrosis Involvement in Osteoarthritis. Front. Med. 8:684389. https://doi.org/10.3389/fmed.2021.684389
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