Research interests/description of main research theme:
In this 4–year PhD project, you will explore the functional role of a pathogenic B cell population we have discovered in the joints of patients with rheumatoid arthritis (RA). These cells are characterised by their expression of FcRL4, a receptor for IgA immune complexes (IgAIC) and provide a potential link between joint and mucosal inflammation. They are now the focus of a drug development project at the University of Birmingham. You will be working in the context of the prestigious RACE Centre (Research Into Inflammatory Arthritis Centre Versus Arthritis http://www.race-gbn.org/
), funded by Versus Arthritis. While the project will be mainly based in the Rheumatology Research Group at the University of Birmingham, you will also spend time at the University of Newcastle, to gain expertise in flow-cytometric analysis of cell signalling, and at the Kennedy Institute in Oxford to explore the role of autophagy in the biology of FcRL4+ B cells.
Expression of FcRL4 and RANKL identifies a B cell population which accumulates in the inflamed joints of RA patients, where they contribute to bone erosion and autoimmunity (Amara et al., 2017; Yeo et al., 2015; Yeo et al., 2011). FcRL4 was originally identified by its homology to Fc receptors and acts as a low-affinity IgA receptor. We have now shown that in the joints of RA patients, FcRL4+ B cells capture IgAIC. Because of their high level of HLA-DR, CD80 and CD86 expression, they potentially act as antigen presenting cells and we hypothesize that the IgAIC are internalized and protein antigens are processed and presented to T cells. Residence of FcRL4+ B cells within the hypoxic microenvironment of the synovium of RA patients suggests autophagy will be activated. This process can further enhance antigen presentation in B cells (Clarke and Simon, 2019). In this project, we plan to investigate the functional consequences of the interaction of IgAIC with FcRL4+ B cells on their activation, internalisation of IgAIC and presentation of the captured antigens.
Applicants should have a strong background in immunology. They should have a commitment to research in inflammatory diseases and hold or realistically expect to obtain at least an upper second-class degree in a relevant subject.
How to apply
Informal enquiries should be directed to Professor Dagmar Scheel-Toellner ([email protected]
Applications should be directed to Prof Dagmar Scheel-Toellner (email [email protected]
). To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and contact details of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.
Amara, K., E. Clay, L. Yeo, D. Ramskold, J. Spengler, N. Sippl, J.A. Cameron, L. Israelsson, P.J. Titcombe, C. Gronwall, I. Sahbudin, A. Filer, K. Raza, V. Malmstrom, and D. Scheel-Toellner. 2017. B cells expressing the IgA receptor FcRL4 participate in the autoimmune response in patients with rheumatoid arthritis. Journal of Autoimmunity 81:34-43.
Clarke, A.J., and A.K. Simon. 2019. Autophagy in the renewal, differentiation and homeostasis of immune cells. Nature Reviews Immunology 19:170-183.
Yeo, L., H. Lom, M. Juarez, M. Snow, C.D. Buckley, A. Filer, K. Raza, and D. Scheel-Toellner. 2015. Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis. Ann Rheum Dis 74:928-935.
Yeo, L., K.M. Toellner, M. Salmon, A. Filer, C.D. Buckley, K. Raza, and D. Scheel-Toellner. 2011. Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann Rheum Dis 70:2022-2028.