Description du projet
Visualiser le mécanisme d’infection inhabituel de minuscules agents pathogènes fongiques
Les microsporidies minuscules constituent une menace croissante pour la chaîne d’approvisionnement alimentaire mondiale, l’environnement et la santé humaine. Classés parmi les agents pathogènes émergents hautement prioritaires, ces organismes sporulants inhabituels sont des agents pathogènes fongiques opportunistes qui posent également des défis au développement de médicaments. Pour améliorer notre compréhension des caractéristiques biologiques cellulaires au cœur de l’infectiosité des microsporidies, le projet PolTube financé par l’UE développera un modèle structurel et mécaniste de leur appareil d’infection, le tube polaire. Plus précisément, il utilisera une approche innovante de techniques de biologie structurelle de pointe et des outils in vivo nouvellement développés pour étudier la structure et la fonction du tube polaire microsporidien. Le résultat sera un modèle architectural de l’organite d’invasion, qui mettra en lumière la spécialisation évolutive unique de ces organismes peu étudiés et fournira de nouveaux outils pour la recherche sur les microsporidies.
Objectif
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.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesmicrobiologymycology
- natural sciencesbiological scienceszoologymammalogy
- natural sciencesbiological sciencesmolecular biologystructural biology
- natural sciencesbiological sciencesgeneticsgenomeseukaryotic genomes
Mots‑clés
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
901 87 Umea
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