Descrizione del progetto
Profilare un misterioso «guerriero» naturale per contrastare la resistenza agli antimicrobici
Intorno a noi si svolgono battaglie complesse tra gli organismi monocellulari, i batteri e i virus che li «mangiano» (batteriofagi), in gran parte sconosciuti alla persona media. Dal momento che la resistenza antimicrobica crea una sfida sempre crescente alla salute pubblica, lo sfruttamento di questi assassini batterici naturali diventa una strada promettente verso nuove terapie. Il problema è che, sebbene i batteriofagi siano gli organismi più abbondanti nella biosfera, ne abbiamo isolati pochissimi e abbiamo ben poca idea di come funzionano. Tutto questo sta per cambiare grazie al progetto PHARMS finanziato dall’UE. Gli scienziati hanno piani ambiziosi per trovare tutti i possibili fagi di un isolato batterico resistente, caratterizzare i meccanismi d’azione e utilizzare le nuove conoscenze per progettare un kit di strumenti terapeutici basati sui fagi.
Obiettivo
Emergence of antimicrobial resistance (AMR) is a grand scientific challenge of our time that has killed more than 700,000 people worldwide. Phage therapy, a promising complement to antibiotics, utilizes viruses of bacteria (bacteriophages) or phage-derived inhibitors as natural ways to fight AMR. The main obstacles in the clinical application of phage-based AMR therapy are the limited number of phage isolates and the unknown molecular mechanisms of phage-delivered bactericidal action. Building on the recent advances of my group in high-throughput, culture-independent but host-targeted methodologies, PHARMS aims to deploy a revolutionary approach: to screen for all possible phages of a resistant bacterial isolate, characterize multiple lines of their bactericidal functions, and use this information for the design of a whole battery of phage-based therapies that employ multifaceted modes of action.
Using an interdisciplinary research plan, PHARMS will discover phage-specific bactericidal action modes at all possible levels ranging from nucleotide sequence and transcription to translation, in order to elucidate the molecular mechanisms driving phage-mediated inhibition of AMR Acinetobacter baumannii, Helicobacter pylori, & Haemophilus influenzae (WP1). These discoveries, together with novel synthetic biology tools, will enable us to engineer an array of phage vectors that mimic phage-deployed bactericidal modes discovered under WP1, including transport of alien genes to deliver bactericidal effects (WP2). PHARMS will provide molecular confirmation and in vitro & in vivo validation of the functions of phage-encoded bactericidal peptides and enzymes (WP3). By elucidating universal and specific mechanisms of phage-delivered inhibition of AMR pathogens, PHARMS is positioned to provide the rational framework for the design of novel therapeutic strategies aimed at treating common and life-threatening infectious diseases.
Campo scientifico
- natural sciencesbiological sciencessynthetic biology
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
85764 Neuherberg
Germania