Descrizione del progetto
Interconnessione tra risposta metabolica e immunitaria nel corso della tubercolosi
La tubercolosi (TBC) costituisce un grave problema sanitario in tutto il mondo. I promettenti trattamenti della TBC con terapie dirette all’ospite richiedono una comprensione completa dell’impatto esercitato dalle interazioni ospite-patogeno sulle vie di segnalazione e sulle risposte cellulari legate all’esito della malattia. La riprogrammazione metabolica delle cellule immunitarie che si verifica durante l’infezione si traduce in glicolisi attiva e produzione di lattato. Quest’ultimo è una molecola di segnalazione a cui i macrofagi possono rispondere attraverso diversi trasportatori. L’obiettivo del progetto Lac-TB, finanziato dall’UE, è quello di studiare l’interconnessione tra la risposta metabolica e quella immunitaria durante l’infezione da TBC, con particolare attenzione alle risposte dei macrofagi al lattato. Il progetto ha il potenziale di identificare nuovi bersagli terapeutici immuno-metabolici dell’ospite per la TBC.
Obiettivo
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.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
B15 2TT Birmingham
Regno Unito