Metabolic regulation of immune responses during infection.
Lead Research Organisation:
King's College London
Department Name: Immunology Infection and Inflam Diseases
Abstract
Effective immune responses during infection or vaccination require successful activation, differentiation and antibody production by B cells. A key mechanism controlling immune cell activation is cellular metabolism, as regulation of metabolic pathways influences fate choices and the functions of activated immune cells. While the metabolic pathways controlling B cell activation remain poorly understood, recent studies suggest a key role for lipid metabolism in the regulation of B cell responses. Accordingly, highly activated germinal centre B cells show a reprogramming of lipid metabolism with an increase in fatty acid oxidation; while impairment of lipid metabolism results in dysregulated B cell activation. Given the key role of B cells in protective immunity and autoimmune diseases, it is of central importance to understand how metabolic programs are regulated
Unpublished data from our lab demonstrate a unique function for the lipid presenting molecule CD1d in the regulation of cellular lipid metabolism. As CD1d is highly expressed on B cells, we aim to investigate the link between CD1d and B cell metabolism and how this in turn controls B cell activation and antibody production.
Aim of the investigation:
Investigating the mechanisms controlling B cell activation
Proposed plan of work:
Year 1/2. We will use a combination of next-generation sequencing and lipidomics to identify the molecular links between CD1 and lipid metabolism pathways in B cells
Year 2/3. We will take advantage of in vitro cultures and cellular and molecular biology techniques to manipulate lipid metabolism pathways and determine their effect on B cell responses
Year 3/4. We will use transgenic mice and in vivo models of vaccination to uncover the link between B cell metabolism and antibody production.
Unpublished data from our lab demonstrate a unique function for the lipid presenting molecule CD1d in the regulation of cellular lipid metabolism. As CD1d is highly expressed on B cells, we aim to investigate the link between CD1d and B cell metabolism and how this in turn controls B cell activation and antibody production.
Aim of the investigation:
Investigating the mechanisms controlling B cell activation
Proposed plan of work:
Year 1/2. We will use a combination of next-generation sequencing and lipidomics to identify the molecular links between CD1 and lipid metabolism pathways in B cells
Year 2/3. We will take advantage of in vitro cultures and cellular and molecular biology techniques to manipulate lipid metabolism pathways and determine their effect on B cell responses
Year 3/4. We will use transgenic mice and in vivo models of vaccination to uncover the link between B cell metabolism and antibody production.
Organisations
People |
ORCID iD |
Patricia Barral (Primary Supervisor) | |
Thomas Ap Rees (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N013700/1 | 01/10/2016 | 30/09/2025 | |||
2605418 | Studentship | MR/N013700/1 | 01/10/2021 | 30/09/2025 | Thomas Ap Rees |