The University of Manchester
About the Project
The implementation of biological therapies has significantly advanced the management of autoimmune diseases (AIDs). However, the failure to achieve clinical remission in ‘non-responders’ remains a significant and unmet challenge. B cells are central to the immunopathogenesis of AIDs. Alterations in B cell phenotype and function have been described in several AIDs, with one key feature being the dysregulation of the regulatory B cell compartment.
Regulatory B cells (Bregs) modulate immune responses via several mechanisms, although primarily via the secretion of IL-10. Their importance in the maintenance of immune homeostasis has been highlighted not only in AIDs but also in other immune-mediated pathologies, including cancers and chronic infections. In the context of AIDs, numerical or/ and functional abnormalities in Bregs have been described across several diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS), and found to be associated with disease severity1. Importantly, the ability of B cells to secrete IL-10 has also been associated with treatment response2,3.
Despite a continuous effort towards understanding Breg biology, identity and function in healthy individuals, the mechanisms promoting loss of Breg function in AIDs remain unknown. The goal of this project is to uncover the signals driving the loss of human Breg function in AIDs (SLE and RA), and to develop disease relevant in vitro “loss of function” culture systems that would provide new opportunities to develop and test B cell-targeted therapies.
The project, using blood samples from healthy controls/ patients, will involve several cutting-edge techniques, including single-cell transcriptomics and proteomics, in addition to flow cytometry, mass spectrometry, LegendPlex bead-based immunoassays and complex in vitro cell culture assays. The student will also gain interdisciplinary skills in bioinformatics and complex disease aetiolog.
Eligibility
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
To be considered for this project you MUST submit a formal online application form – full details on how to apply can be found on the MRC DTP website https://www.bmh.manchester.ac.uk/study/research/mrc-dtp/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
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