Description du projet
Le rôle du microenvironnement dans le résultat des maladies infectieuses
Du fait d’une hausse rapide de la résistance aux antibiotiques, il est nécessaire de découvrir de nouveaux médicaments ou de nouvelles stratégies afin de contrôler les maladies infectieuses. La compréhension de l’interaction entre l’hôte et l’agent pathogène et de l’influence du microenvironnement tissulaire aidera les scientifiques à découvrir de nouvelles cibles pour les interventions. Le projet SalPhagoHet, financé par l’UE, utilisera Salmonella enterica pour étudier les propriétés immunitaires des neutrophiles et des macrophages présents dans les tissus dans différents environnements. En utilisant la protéomique, les scientifiques détermineront les facteurs clés requis pour la phagocytose par ces cellules immunitaires, ainsi que les réponses des agents pathogènes. Les résultats permettront de révéler les niches permissives dans lesquelles les agents pathogènes survivent et se propagent.
Objectif
Infectious diseases represent a major threat to global human health today. Antibiotic misuse has induced rapid emergence of resistant bacteria and it is becoming increasingly challenging to identify new, efficient drugs. Novel control strategies are urgently required. This project intends to uncover key host immune factors determining the outcome of a bacterial infection with the aim to identify strategies to synergise with the immune system. Emerging evidence suggests that heterogeneous host-pathogen encounters play a key role in disease outcome. To investigate the role of distinct tissue microenvironments during infection, I will use Salmonella enterica to study the immune properties of neutrophils and resident tissue macrophages, previously shown to be non-permissive and permissive environments, respectively. Specifically, I will use a novel approach of phagosome isolation by fluorescence-activated cell sorting and will combine it with sensitive high-resolution mass spectrometry. With this state-of-the-art technology, I will identify key host factors required for phagosome formation by proteomics, which will provide relevant insights into the biology of two key professional phagocytes with important applications in infection biology and immunology. Secondly, I will analyse Salmonella responses to these host determinants using proteomics and stress-inducible promoter fusions to reporter genes. This will highlight key bacterial strategies for intracellular survival and thus novel antimicrobial targets. Finally, I will confirm the in vivo role of identified key factors using a murine infection model. This integrated approach, investigating the host and the pathogen, will be broadly applicable to study other important infectious diseases. This project will highlight specific host and pathogen responses with the aim to close permissive niches where suboptimal antimicrobial exposure allows pathogens to survive and spread.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesbasic medicineimmunology
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
NE1 7RU Newcastle Upon Tyne
Royaume-Uni