Descrizione del progetto
Visualizzare l’insolito meccanismo di infezione di minuscoli patogeni fungini
I minuscoli microsporidi rappresentano una minaccia crescente per la filiera alimentare globale, l’ambiente e la salute umana. Questi insoliti organismi che formano spore, classificati come patogeni emergenti di priorità elevata, sono patogeni fungini opportunisti che pongono sfide anche allo sviluppo di farmaci. Per migliorare la nostra comprensione in merito alle caratteristiche biologiche delle cellule che sono centrali per l’infettività dei microsporidi, il progetto PolTube, finanziato dall’UE, elaborerà un modello strutturale e meccanicistico del loro apparato di infezione, il tubo polare. In particolare, utilizzerà un approccio innovativo di tecniche di biologia strutturale all’avanguardia e strumenti in vivo sviluppati di recente per studiare la struttura e la funzione del tubo polare dei microsporidi. Il risultato sarà un modello architettonico dell’organello di invasione, che farà luce sulla specializzazione evolutiva unica di questi organismi poco studiati e fornirà nuovi strumenti per la ricerca sui microsporidi.
Obiettivo
Microsporidia are opportunistic fungal pathogens that infect organisms as evolutionarily divergent as protists and mammals. Due to their growing impact on the global food supply chain, the environment, and human health, these unusual spore-forming organisms have been classified as emerging pathogens of high priority. Intriguing cell biological features that are central to microsporidian infectivity and pose challenges to drug development are poorly understood due to a lack of structural information and the absence of genetic tools. As energy parasites, microsporidia survive with the smallest eukaryotic genome and without classical mitochondria through an obligate intracellular lifestyle. A fascinating infection mechanism, which involves a long, hollow protein structure, is essential for efficient host invasion. The microsporidia-specific infection apparatus consists of several structural proteins that form the polar tube, which is used to inject the entire cytoplasm from the infectious spore into the host cell. Here, we will use an innovative approach to provide the structural and mechanistic basis of the microsporidian infection mechanism by using cutting-edge structural biology techniques and novel developed in-vivo tools. By studying the endogenous polar-tube, we will identify new elements and provide an architectural model of the invasion organelle. Reconstitution and biochemical characterization of the major components of the polar tube, followed by high-resolution cryo-EM studies, will unravel the polar tube protein interaction network and provide near-atomic information to complement the architectural model. Together with the development of genetic methods to tag, visualize and manipulate components in-vivo, we will provide a comprehensive model of the infection process, give insights into the specialization and evolution of a fascinating and understudied organism and deliver ground-breaking tools to open new frontiers in microsporidian research.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesmicrobiologymycology
- natural sciencesbiological scienceszoologymammalogy
- natural sciencesbiological sciencesmolecular biologystructural biology
- natural sciencesbiological sciencesgeneticsgenomeseukaryotic genomes
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
901 87 Umea
Svezia