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Development of a high throughput butyrophilin analysis, to complement a holistic immunological analysis tool for clinical diagnosis/prediction of prognosis

  • Full or part time
  • Application Deadline
    Wednesday, January 01, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Working with Nonacus Ltd with Coeliac UK/ Innovate UK and MRC funding, we have developed a high throughput capture-based sequencing tool for T-cell and B-cell receptor repertoire, together with a bioinformatic algorithm, which can be used to diagnose immune/ inflammatory conditions (e.g., coeliac disease and inflammatory bowel disease) in patient biopsy samples, as an alternative to biopsy examination under the microscope. We are also testing our pipeline as an early diagnostic test for cancer and lymphoma and as a predictor of cancer prognosis and/ or response to immunomodulatory therapy.

Because T-cells recognise antigens in the context of a particular HLA type, we include HLA typing in our capture/ analytical pipeline. For coeliac disease, for example, which is tightly associated with HLA-DQ2/8, this is very important diagnostically. As we expand this clinical diagnostic/ predictive approach to more conditions, we recognise the utility of interrogating additional analogous immune loci, in particular the highly polymorphic butyrophilin system, which is important in modulating gamma/delta T-cell function. Recent data shows a lack of expression of a butyrophilin family member, BTNL8, in small intestine in coeliac disease, a condition driven by gamma/delta T-cells, and the exact mechanisms controlling this loss of expression remain unclear.

We now wish to develop a capture-based system for butyrophilin analysis to add to our pipeline. We will initially use this to determine the association of butyrophilin family polymorphisms/ deletions with various pathologies, aiming to develop new clinical assays for diagnosis and prediction of prognosis in immunologically mediated/ modulated conditions.

Funding Notes

Funding* will cover the student’s stipend at the current Research Council rate and University Fees. The studentships will be funded for three years in the first instance subject to eligibility**, with the possibility of additional funding in the fourth year depending on circumstances.

**The studentships are available to students who qualify for Home/EU fees

Applications from ineligible candidates will not be considered.

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References

Roberts, T., Huang, Y., Bibawi, H., Matharu, B., Bench, A., Scott, M., Liu, H. Contribution of immunoglobulin lambda light chain gene rearrangement analysis in the diagnosis of lymphoproliferative disorders. British Journal of Haematology (2019) 185(2):261-265.
2. Colling, R., Wang, L.M., Soilleux, E. Validating a fully automated real-time PCR based system for use in the molecular diagnostic analysis of colorectal carcinoma: a comparison with NGS and IHC. Journal of Clinical Pathology. (2017) 70(7):610-614.
3. Colling R., Royston, D., Soilleux E. The role of clonality studies in diagnostic molecular haematopathology. Journal of Hematopathology. (2016) 8;9(3):143-147

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