Ultra-high throughput analysis of immunoglobulin repertoires in health and autoimmune disease
- Project No: NCKIR6
- Intake: 2022 KIR Non Clinical
Supervisor: Prof. Lynn B. Dustin
Co-Supervisor: Prof. John Frater (Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research)
Rheumatic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and Sjögren’s syndrome are associated production of specific autoantibodies. The reasons for failure of immune tolerance to a finite number of autoantigens are poorly understood. Using a bespoke microfluidics platform, the supervisors have developed a workflow to sequence paired immunoglobulin heavy and light chain genes for hundreds of thousands to millions of B cells in a single blood sample. The student will use this platform to characterise the full immunoglobulin repertoire of naïve, activated, and antibody-secreting B cell subsets in the peripheral blood in samples from patients with autoimmune disease, compared to the same B cell subsets in healthy donors. This work will lead to a valuable atlas of immunoglobulin repertoire breadth at different stages of the B cell lifespan and will help to identify the points at which self-tolerance may fail in autoimmune disease.
Immunology, Immune repertoire, autoimmune disease, bioinformatics, microfluidics
Microfluidics, flow cytometry, fluorescence-activated cell sorting, bioinformatics, molecular biology
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- Charles ED, Brunetti C, Marukian S, Ritola KD, Talal AH, Marks K, Jacobson IM, Rice CM, Dustin LB. Clonal B cells in patients with hepatitis C virus-associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset. Blood. 2011 May 19;117(20):5425-37. doi: 10.1182/blood-2010-10-312942. Epub 2011 Mar 18. PMID: 21421840; PMCID: PMC3109715.
- Charles ED… Dustin LB. Somatic hypermutations confer rheumatoid factor activity in hepatitis C virus-associated mixed cryoglobulinemia. Arthritis Rheum. 2013 Sep;65(9):2430-40. doi: 10.1002/art.38041. PMID: 23754128; PMCID: PMC4026862.
Immunology, Bioinformatics, Autoimmune Disease