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Our aims are to understand B cell development and diseases associated with abnormal antibody production. Inadequate or excessive immune responses lead to immunodeficiency or autoimmune and inflammatory diseases, which place a major economic and social burden on world health and the quality of human life. So, we are interested in the normal processes of immune function and how individuals vary due to inherited or acquired differences.

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B cell development: modelling immunodeficiency. Much of our knowledge about immune control has come from studying rare mouse and human mutations. We are collaborating with groups in the University of Newcastle and elsewhere to study Human Mendelian mutations leading to immunodeficiency. Our latest projects involve using CRISPR/Cas9 homologous replacement in zygotes to model human disease.

B cell selection: modelling autoimmunity and self-tolerance. We use transgenic models and other basic immunological assays to study antigen-specific B cells. This approach makes it possible for us to compare uniform populations of cells from mice with specific mutations affecting lymphocyte regulation, and track the response to foreign antigens and movement of antigen-specific cells in vivo. Current projects investigate how the immune system regulates the response to different forms of antigen and how B cells are positively selected into the naïve repertoire during ontogeny.

Immune Regulation: developing novel therapeutics. Our final approach is to develop novel antibody-based therapeutics, which will reduce the immune or inflammatory response in human disease. This project, which is a longstanding collaboration with Professor Simon Davis at Oxford, targets superagonists against human leukocyte inhibitory receptors. To accelerate this work, we have developed a series of mice carrying human receptors.

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Selected publications

Collaborators

Prof Sophie Hambleton – Newcastle University

Prof Moin Saleem – Bristol University

Prof Jason Cyster – UCSF

Dr Paul Love – NIH

Dr Helen Su – NIH

Lab alumni (Former DPhil students)

Helen Ferry

Janson Leung

Karlee Silver

Anastasiya Nyzhnyk

Andy Johnson

Billur Akkaya

Greg Crawford

Owen Siggs

Daian Cheng

Katherine Bull

Current grants

2017-2022: The Identification of Pathways involved in immune regulation and B cell selection. MRC Human Immunology Unit, Oxford. £1,400,000 for 5 years.

2013-2018: Co-principal Investigator, Wellcome Trust Strategic Award, 3i. Jointly £4,000,000 for 5 years.

2015-2018: B cell receptor triggering. MRC Clinical Training Fellowship, Martin Wilcock, £218,258

2015-2018: Superagonists. Wellcome Trust Clinical Training Fellowship, Chris Paluch, £250,316

2018-2022: An investigation into the genetic and functional basis of proteinuria kidney disease, MRC Career Development Fellowship, Katherine Bull