Obiettivo Over the next 35 years, antibiotic resistant bacteria are expected to kill more than 300 million people. The need to find alternative strategies for antimicrobial therapies remains a global challenge with several bottlenecks in the antibiotic discovery process. Using Staphylococcus aureus, the most common multidrug-resistant bacterium in the European Union and an excellent model organism for cell division in cocci, we propose: (i) to find new pathways to re-sensitize resistant bacteria. Bacteria undergo major morphology changes during the cell cycle. We hypothesize that these changes generate windows of opportunity during which bacteria are more susceptible or more tolerant to the action of antibiotics. We will identify key regulators of the cell cycle in order to manipulate the duration of windows of opportunity for the action of existing antibiotics. (ii) to develop new fluorescence-based reporters for whole-cell screenings of antimicrobial compounds with new modes of action, including compounds that arrest or delay the cell cycle; compounds that target non-essential pathways that are required for expression of resistance against existing antibiotics and therefore can be used as synergistic drugs for combination therapies; compounds that inhibit the production of virulence factors and compounds that revert persister states that are phenotypically resistant to antibiotics. (iii) to unravel new modes of action of antibiotics by using the constructed reporter strains as powerful tools to learn how antibiotics act at the single cell level.Over the past years, my group has become expert on the biology of S. aureus, has constructed powerful biological tools to study cell division and synthesis of the cell surface and has studied mechanisms of action of various antimicrobial compounds. We are therefore in a privileged position to quickly unravel the function of new players in the bacterial cell cycle and simultaneously contribute to accelerate antibiotic discovery. Campo scientifico natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencescell biologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2017-COG - ERC Consolidator Grant Invito a presentare proposte ERC-2017-COG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante UNIVERSIDADE NOVA DE LISBOA Contribution nette de l'UE € 2 533 500,00 Indirizzo CAMPUS DE CAMPOLIDE 1099 085 Lisboa Portogallo Mostra sulla mappa Regione Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione 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 € 2 533 500,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto UNIVERSIDADE NOVA DE LISBOA Portogallo Contribution nette de l'UE € 2 533 500,00 Indirizzo CAMPUS DE CAMPOLIDE 1099 085 Lisboa Mostra sulla mappa Regione Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione 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 € 2 533 500,00
