Obiettivo Cell-autonomous immunity is the ability of a host cell to eliminate an invasive infectious agent. Recent work has shown that components of the cytoskeleton have a major role in cell-autonomous immunity and control of bacterial infection. The Mostowy group has shown that some intracellular bacteria, including Shigella flexneri and Mycobacterium marinum, can escape from phagosomes and invade the host cell cytosol where they interact with cytoskeleton components to form actin tails or be entrapped in septin cage-like structures. However, our knowledge of these interactions derives from a limited number of in vitro studies, and has not been fully characterized in vivo during a disease-causing infection. M. marinum, a species closely related to the human pathogen M. tuberculosis, can be applied as a paradigm to understand the cell biology of mycobacterial infection. Zebrafish is naturally susceptible to M. marinum and, as I have shown during my PhD, can be used as an important animal model to gain in-depth information about the innate immune response to bacterial infection. Using state-of-the-art genome editing tools and high resolution microscopy techniques, I will study M. marinum interactions with the cytoskeleton, and investigate the role of these interactions in cell-autonomous immunity. Using M. marinum, my specific objectives are: 1) to identify and characterize host and pathogen determinants affecting autophagy-cytoskeleton interactions, and 2) to investigate the discovered molecules and mechanisms in vivo using the zebrafish model. A more comprehensive understanding of M. marinum-cytoskeleton interactions will have important consequences for enhancing host defense and fighting antimicrobial resistance. This should provide vital clues towards new strategies aimed at combating infectious diseases, and possibly other human diseases that arise from a dysfunctional host response. Campo scientifico medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health scienceshealth sciencesinflammatory diseasesmedical and health scienceshealth sciencesinfectious diseasesmedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2015 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-ST - Standard EF Coordinatore IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Contribution nette de l'UE € 183 454,80 Indirizzo SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Regno Unito Mostra sulla mappa Regione London Inner London — West Westminster Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 183 454,80
