We (https://sansomlab.org) are investigating the cellular and molecular basis of inflammatory arthritis. This research project is focussed on ankylosing spondylitis (AS), a common and highly heritable form of arthritis which characteristically involves inflammation of the sacroiliac joints and spine. To understand the causes of this disease we are using multi-modal single-cell genomics approaches (including transcriptomics and CITE-seq) to generate detailed maps of patient biopsy samples.
This work is important as current therapeutics do not work in all patients and cannot induce disease remission. Inflammation in AS is known to involve the IL-23/IL-17 immune pathway but the molecular origins of the disease remain mysterious. The strong genetic association of AS with the human leukocyte antigen (HLA) class I molecule HLA-B*27 (odds ratio=131) suggests that inflammation is triggered by an ‘arthritogenic’ peptide, but there is also evidence for several other models of disease pathogenesis. Our hypothesis is that the disease involves the dysregulation of a homeostatic tissue repair circuit (comprised of immune and stromal cells) at sites where muscle is anchored in bone (entheses).
In order to discover disease-specific changes in cellular composition and phenotype the single-cell datasets from AS will be compared with those from other types of arthritis (such as rheumatoid arthritis) and healthy joints (which we are generating as part of the Human Cell Atlas project; https://www.humancellatlas.org/). Spatial analysis and data from genome wide association studies (GWAS) will be used to help pin-point pathogenic cell types. You will collaborate closely with a team of clinical and experimental colleagues that is led by Professor Paul Bowness. The project team will validate and test findings in follow-up experiments using approaches such as CyTOF and CRISPR-based gene editing.
Ultimately, the results of this research will provide a rational basis for the development of more effective therapeutics that target the causes, rather than the symptoms, of AS. This work is supported by funding from Versus Arthritis.
You will lead the computational analysis and interpretation of the single cell datasets with the goal of discovering the cells, inter-cellular signalling circuits, biological pathways and genes that are responsible for causing disease. To do so you will work closely with a team of clinicians and experimental scientists.
- To perform scientific research, reviewing and refining working hypotheses, and developing and acquiring relevant skills.
- To analyse and interpret data, preparing and publishing your findings in peer-reviewed journals.
- To actively participate in the broader research team, working closely with clinical and experimental colleagues to share data and findings and help design experiments.
- To communicate results in regular meetings, by poster and oral presentations at scientific meetings, or via other suitable means.
- To write and maintain software pipelines and programs, adapting existing and developing new scientific methods for data analysis.
- To identify training needs and to follow an agreed strategy to meet them.
- To act as a source of information and advice to other members of the group, training and supervise graduate and undergraduate students as appropriate.
- To keep abreast of the relevant literature and methodological developments and to contribute ideas for new research projects.
- To maintain, curate and disseminate the single cell genomics data, submitting it to online databases such as e.g. the Human Cell Atlas data portal as appropriate.
- To manage own academic research and administrative activities. This involves small scale project management, to co-ordinate multiple aspects of work to meet deadlines.
- The Postdoctoral Fellow will be a member of the Computational and Single Cell Genomics team led by Dr Stephen Sansom at the KIR.
- The post-holder will work closely with clinical and experimental colleagues in the research group of Professor Paul Bowness.
- The post-holder will also work with colleagues in the Human Cell Atlas Joint consortium (co-led by Dr Stephen Sansom and Professor Chris Buckley).
All offers of employment are made subject to standard pre-employment screening, as applicable to the post.
If you are offered the post, you will be asked to provide proof of your right-to-work, your identity, and we will contact the referees you have nominated. You will also be asked to complete a health declaration (so that you can tell us about any health conditions or disabilities so that we can discuss appropriate adjustments with you), and a declaration of any unspent criminal convictions.
We advise all applicants to read the candidate notes on the University’s pre-employment screening procedures, found at: www.ox.ac.uk/about/jobs/preemploymentscreening/.
Additional security pre-employment checks
Due to the nature of the research at the Kennedy Institute of Rheumatology, this job will require additional security pre-employment checks:
- A satisfactory basic Disclosure and Barring Service check