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Dissecting the impact of Lactate in Tuberculosis

Project description

Metabolic and immune responses crosstalk in the course of tuberculosis

Tuberculosis (TB) is a major health problem worldwide. Promising TB treatments with host-directed therapeutics require a comprehensive understanding of host-pathogen interactions' impact on signalling pathways and cellular responses related to disease outcome. Metabolic reprogramming of immune cells that occurs during infection results in active glycolysis and lactate production. Lactate is a signalling molecule, and macrophages can respond to it through different transporters. The goal of the EU-funded Lac-TB project is to investigate the crosstalk between metabolic and immune responses during TB infection with a particular focus on the macrophage responses to lactate. The project has the potential to identify new host immune-metabolic therapeutic targets for TB.

Objective

Tuberculosis (TB) is a major global public health problem in which one-fourth of the world’s population is latently infected. Host-directed therapeutics are a promising approach; however, we require a comprehensive understanding of how host-pathogen interactions impact signalling pathways and cellular responses to dictate disease outcome.
Metabolic reprogramming of immune cells has been described during Mycobacterium tuberculosis (M.tb) infection, resulting in active glycolysis and lactate production. Lactate is an active signalling molecule and macrophages, the main M.tb cell target, can respond to it through different transporters.
The main aim of this project is to investigate the crosstalk between metabolic and immune responses in the context of M.tb infection, with a particular focus on macrophage responses to lactate. This project has the potential of revealing new host immune-metabolic therapeutic targets for TB disease.
Birmingham has one of the highest rates of TB in the UK and University of Birmingham (UoB) is a world-reference institution for metabolic and metabolomic studies. Dr Llibre has a strong background in immunology and moving to Dr Mauro’s laboratory at UoB will provide her with a rare opportunity to obtain a unique skillset, allowing her to study cell metabolism in high resolution. The expertise, facilities and supervisory team at the host institution, together with Dr Llibre’s extensive knowledge on immunology and infectious disease ensure the feasibility of this project. UoB will provide Dr Llibre a privileged environment to fully develop all the skills required to lead a successful research group, including training in scientific communication; opportunities for supervising and teaching, for learning how to coordinate a project and protect intellectual property. At the end of the fellowship, Dr Llibre will be at the forefront of the much needed and exciting field of immuno-metabolism, equipped to secure funding as an independent researcher.

Coordinator

THE UNIVERSITY OF BIRMINGHAM
Net EU contribution
€ 224 933,76
Address
Edgbaston
B15 2TT Birmingham
United Kingdom

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Region
West Midlands (England) West Midlands Birmingham
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 224 933,76