Descrizione del progetto
Il ruolo del microambiente nel decorso delle malattie infettive
La resistenza agli antibiotici è in rapida crescita, il che rende necessaria la scoperta di nuovi farmaci o strategie per controllare le malattie infettive. Comprendere l’interazione tra ospite e agente patogeno, oltre all’influenza del microambiente tissutale, aiuterà gli scienziati a scoprire nuovi bersagli per l’intervento. Il progetto SalPhagoHet, finanziato dall’UE, utilizzerà la salmonella enterica per studiare le proprietà immunitarie dei neutrofili e dei macrofagi tissutali residenti in ambienti differenti. Avvalendosi della proteomica, gli scienziati stabiliranno i fattori chiave necessari per la fagocitosi da parte di queste cellule immunitarie, nonché le risposte degli agenti patogeni. I risultati riveleranno nicchie di tolleranza in cui gli agenti patogeni possono sopravvivere e diffondersi.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesbasic medicineimmunology
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
NE1 7RU Newcastle Upon Tyne
Regno Unito