Descripción del proyecto
Visualización del mecanismo de infección poco común de unos patógenos fúngicos diminutos
Los diminutos microsporidios son una amenaza creciente para la cadena agroalimentaria mundial, el medio ambiente y la salud humana. Clasificados como patógenos de nueva aparición de alta prioridad, estos organismos poco comunes que forman esporas son patógenos fúngicos oportunistas que también plantean problemas para el desarrollo de fármacos. Para mejorar nuestra comprensión de las características biológicas de las células que son fundamentales para la infecciosidad microsporidia, el proyecto financiado con fondos europeos PolTube desarrollará un modelo estructural y mecanicista de su órgano de infección, el tubo o filamento polar. En concreto, utilizará un método innovador de técnicas de biología estructural de vanguardia y herramientas «in vivo» recién desarrolladas para estudiar la estructura y la función del filamento polar de los microsporidios. El resultado será un modelo estructural del orgánulo de invasión, que arrojará luz en la especialización evolutiva singular de estos organismos infraestudiados y proporcionará nuevas herramientas para la investigación de los microsporidios.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesmicrobiologymycology
- natural sciencesbiological scienceszoologymammalogy
- natural sciencesbiological sciencesmolecular biologystructural biology
- natural sciencesbiological sciencesgeneticsgenomeseukaryotic genomes
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
901 87 Umea
Suecia