Project description
Visualising the unusual infection mechanism of tiny fungal pathogens
Tiny microsporidia are a growing threat to the global food supply chain, the environment, and human health. Classified as emerging pathogens of high priority, these unusual spore-forming organisms are opportunistic fungal pathogens that also pose challenges to drug development. To improve our understanding of the cell biological features that are central to microsporidian infectivity, the EU-funded PolTube project will develop a structural and mechanistic model of their infection apparatus, the polar tube. Specifically, it will use an innovative approach of cutting-edge structural biology techniques and newly developed in vivo tools to study the structure and function of the microsporidian polar tube. The result will be an architectural model of the invasion organelle, which will shed light on the unique evolutionary specialisation of these understudied organisms and provide novel tools for microsporidian research.
Objective
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.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesmicrobiologymycology
- natural sciencesbiological scienceszoologymammalogy
- natural sciencesbiological sciencesmolecular biologystructural biology
- natural sciencesbiological sciencesgeneticsgenomeseukaryotic genomes
Keywords
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Funding Scheme
ERC-STG - Starting GrantHost institution
901 87 Umea
Sweden