About the Project
We study the cellular interactions and molecular events that lead to the development of high affinity and protective antibodies during humoral immune responses. Our main focus is the germinal centre reaction.
The quality of antibodies improves over the course of immune responses due to antibody affinity maturation. This remarkable process occurs within specialised structures, known as germinal centres, that form within B cell follicles of the local secondary lymphoid tissues. Here, B cells “evolve” their antibody genes through the random introduction of somatic mutations, and by selection. Cells with damaging mutations are screened out, while cells carrying nucleotide changes that enhance antibody:antigen binding are preferentially expanded. Despite its fundamental importance in acquired immunity, the events involved in this selection process remain incompletely understood. This is especially true in the context of “real” infections, where antigens are often complex. Most pathogens display a plethora of epitopes and the best neutralization sites are commonly “challenging” targets. For example, broadly neutralising antibodies against HIV develop in germinal centres, but only infrequently, and only after months or years of acquiring mutations. These problems are discussed in more depth in Bannard and Cyster, Curr. Opin. Immunol. 2017 (PMID: 28088708).
Projects in the Bannard laboratory focus around trying to decipher the fundamental biology underpinning the development of humoral immunity. We investigate the cellular interactions and regulatory mechanisms that facilitate antibody affinity maturation. We aim to understand what “selection” entails, and we hope to determine how cells make fate choices such as when to differentiate. To reach these goals, we employ a wide range of cutting-edge techniques such as high-end flow cytometry, confocal microscopy, live cell imaging (e.g. multi-photon), single B cell cloning and next generation sequencing. Our work relies heavily on sophisticated genetically modified in vivo systems and we often use live virus infections (e.g. Influenza A). As such, students can expect to receive sound intellectual and practical science training.
Informal enquiries are welcomed and can be directed to [Email Address Removed].
Project will be based in the Bannard lab in the MRC Weatherall Institute of Molecular Medicine (WIMM). This is a small group and so students will benefit from frequent interactions with their supervisor.
As well as the specific training detailed above, students will have access to high-quality training in scientific and generic skills, as well as access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.
All MRC WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the MRC WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework.
Funding Notes
Our main deadline for applications for funded places has now passed. Supervisors may still be able to consider applications from students who have alternative means of funding (for example, charitable funding, clinical fellows or applicants with funding from a foreign government or equivalent). Prospective applicants are strongly advised to contact their prospective supervisor in advance of making an application.
Please note that any applications received after the main funding deadline will not be assessed until all applications that were received by the deadline have been processed. This may affect supervisor availability.
References
Stewart, I., Radtke, D., Phillips, B., McGowern, S. & Bannard, O. (2018) Germinal Center B Cells Replace Their Antigen Receptors in Dark Zones and Fail Light Zone Entry when Immunoglobulin Gene Mutations are Damaging. Immunity, 18;49(3):477-489.
Bannard, O., and Cyster, J.G. (2017). Germinal centers: programmed for affinity maturation and antibody diversification. Curr. Opin. Immunol. 45, 21–30.
Bannard, O., McGowan, S.J., Ersching, J., Ishido, S., Victora, G.D., Shin, J.-S., and Cyster, J.G. (2016). Ubiquitin-mediated fluctuations in MHC class II facilitate efficient germinal center B cell responses. J. Exp. Med. 213, 993–1009.
Bannard, O., Horton, R.M., Allen, C.D.C., An, J., Nagasawa, T., and Cyster, J.G. (2013). Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection. Immunity 39, 912–924.
Bannard, O., Kraman, M., Fearon, D.T. (2009). Secondary replicative function of CD8+ T cells that had developed an effector phenotype. Science, 323(5913):505-509.
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