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Metabolic microenvironments in humoral immunity

Project description

Exploring the metabolism of immune cells

The immune system is a complex network of organs, cells and proteins that defends the body against infection. Specialised cells in the immune system can adapt to the body’s changing conditions. These adaptations take place within highly organised tissue microenvironments, where shifts in nutrient and energy availability guide their behaviour. The ERC-funded MicroMeta project aims to study changes in immune cell metabolism. It will focus on the germinal centres in lymphoid tissue that contain B cells that proliferate to produce high-affinity antibodies. The project will cover responses in autoimmune diseases like systemic lupus erythematosus.

Objective

Immune responses occur in often highly compartmentalised tissue microenvironments, which in turn
define local metabolic conditions. In the architecture of lymphoid tissue, very little is known about
cellular metabolic interactions, or how immune cells adapt their metabolism in response to a changing
environment. The humoral immune response is essential for normal immunity, and its centrepiece is
the germinal centre (GC) reaction, which allows the generation of high-affinity antibodies and B cell
memory. The GC is tightly spatially organised in lymphoid tissue, but how this microenvironment
shapes the metabolism of GC B cells is unknown. In this project, we will explore two fundamental
questions in B cell metabolism. GC B cells, despite dividing at the highest rate of any cell, have a
highly distinct metabolism dependent on OxPhos. Yet, the processes which maintain this are poorly
understood. We will examine the role of dynamic mitochondrial morphology in GC homeostasis, using
comprehensive metabolic and immune phenotyping across multiple genetic models. In the second
aim, we will explore the effect and sensing of environmental metabolites on GC function, and how
stromal cells actively regulate their metabolic microenvironment, in both health and the autoimmune
disease systemic lupus erythematosus.

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(opens in new window) ERC-2025-COG

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Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 990 728,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 990 728,00

Beneficiaries (1)

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