About the Project
Project description
Degenerative spinal deformity encompasses degenerative scoliosis and sagittal deformity with spinal imbalance and commonly presents as a combination of the two. While degeneration of the spine is part of the ageing process, the development of a spinal deformity as a result represents unfavourable ageing as disc degeneration should ideally result in a straight and stiff spine. Asymmetric disc degeneration can result into translation of vertebral bodies and a curvature (scoliosis) which often results into compression of spinal nerves and/or spinal stenosis. Unfavourable degeneration can also result into a loss of the physiologic curvatures of the spine in the sagittal plane and subsequent spinal imbalance. Patients fall forward and an upright posture is not possible anymore and associated with significant pain and limitations in every day life. The imbalance of the spine has been shown to be more strongly associated with pain and disability than the scoliosis component of the deformity.
The European Spine Study Group has established that adult spinal deformity presents a significant and relevant disease burden to patients comparable to other chronic diseases such as chronic lung disease, congestive heart failure or arthritis and suggested that research into pathogenesis and treatment is imminently required given the growing ageing population. Understanding what may trigger unfavourable degeneration may open possibilities for early treatment, because surgical treatment of a fully established degenerative spinal deformity is associated with a high complication rate, peri-operative morbidity and healthcare costs.
Little is known about the pathogenesis of adult degenerative spinal deformity, and in particular why some spines remain straight with ageing and degeneration and why others degenerate asymmetrically and gradually collapse. Factors such as life-style, intrinsic factors and hormonal or genetic factors have been suggested to affect the development of a degenerative spinal deformity. Studies have found asymmetric paravertebral muscle atrophy in patients with degenerative scoliosis or have suggested copy number variation of a number of genes specific to degenerative scoliosis or gene polymorphisms such as for example in NMDA (N-methyl-D-aspartate) receptor genes or synaptic membrane exocytosis 2 genes, suggesting that gene polymorphisms may contribute to the development of a degenerative scoliosis.
In this project we aim to use the UK Biobank prospective cohort, with its unique general population of 100,000 participants’ spinal images to correlate genotypes to clinical phenotypes of adult degenerative scoliosis and analyse the downstream implications of the different genotypes on cellular metabolism and resulting tissue mechanics. The imaging, biological samples and relevant clinical and personal data are already available and, or on track to be collected. There should be no barriers to access to these data based on our experience. Thus this presents a phenomenal opportunity to address a big question with a large high quality dataset that cannot be easily replicated elsewhere internationally, guaranteeing substantial interest in the outcome. The project involves computer-based image analysis to identify individuals with lumbar scoliosis on their DEXA scans (http://biobank.ctsu.ox.ac.uk/crystal/label.cgi?id=125 ) for bone density measurements. In a second step, we aim to correlate genotypic information in the UK Biobank to the clinical phenotypes and compare to a control group and then study the implications on cellular metabolism and tissue metabolism or matrix-turnover.
In this DPhil project, the student will be guided to achieve the following tasks:
Year 1: supervised literature review and supervised development of computer-based screening for scoliosis on DEXA scans.
year 2: Analysis and correlation of UK Biobank genotypes to degenerative scoliosis in collaboration with Prof. Furniss’ group
year 3: Analysis of gene expression in relation to identified genotypes versus control groups
Details of the research group
The DPhil will be a joint activity between Spinal Research, with supervision from both Dr Rothenfluh and Prof Silman https://www.ndorms.ox.ac.uk/research/Musculoskeletal-Pharmacoepidemiology) and the Genetics and Epidemiology of Common Hand Disorders: Prof Furniss (https://www.ndorms.ox.ac.uk/research/Genetics-and-epidemiology-of-common-hand-conditions) groups. Dr Rothenfluh is an internationally recognised spinal surgeon researching on the relation of spinal degeneration to adult spinal deformity. Prof Silman is a highly experienced researcher, was on the steering committee that designed UK Biobank and supervisor of projects emerging of. Associate Prof Furniss is an academic hand surgeon with expertise in the use of ‘big data’ and genetics, specifically the UK Biobank genetic data.
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 relevant related research methodology, including the handling and analysis of large datasets, and advanced statistical techniques. Attendance at formal training courses will be encouraged, and will include the “Real world epidemiology Oxford summer school” and the “Advanced musculoskeletal epidemiology UK-RIME summer school”. In addition, courses from the Oxford Learning Institute and the Oxford University Computer Sciences on key skills for the completion of a successful PhD thesis will be available. Additional on the job training opportunities will arise, and the supervisors will encourage the student to pursue such opportunities for data analysis and wet lab techniques such as gene expression analysis.
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 and data analysis.
Students will attend weekly seminars within the department and those relevant in the wider University.
Students will be expected to present data regularly to the department, the research and to attend external conferences to present their research globally.
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 Directors of Graduate Studies 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, and will also need to provide evidence of English language competence. The University requires candidates to formally apply online and for their referees to submit online references via the online application system.
The application guide and form is found online and the DPhil or MSc by research will commence in October 2017.
When completing the online application, please read the University Guide: https://www.ox.ac.uk/admissions/graduate/applying-to-oxford/application-guide?wssl=1