Obiettivo BackgroundHumans and other animals harbour enormous microbial consortia, especially in the lower intestine. My group has now shown that effects of the microbiota on host are far earlier and more pervasive than previously appreciated, starting even before birth from exposure to defined maternal microbial metabolites.ConceptThere is a critical window for development of immunity and metabolism in early life. This shapes infectious resistance, lymphocyte repertoire development and the likelihood of later autoimmune or inflammatory disease. We will determine the molecular mechanisms of how the maternal microbiota prepares the newborn for the critical fetal/suckling/early-independent-nutrition transitions. The core hypothesis is that generally pervasive effects of maternal microbial influences, so-far investigated only for innate immunity and metabolism of germ-free offspring, can be defined in terms of a clear portfolio of maternal microbial molecular signatures and epigenetic marks as the newborn develops with its own microbiota. ApproachInterdependence of microbial ⇄ host interactions during gestation and lactation will be dissected using reversible colonisation systems under axenic and precisely controlled gnotobiotic conditions. The flow and identity of maternal microbial metabolites driving development and shaping incoming colonisation shall be determined from high-resolution metabolomics and host strain combinations that reveal in vivo signalling and epigenetic marks. SignificanceThe project will reveal mechanisms of the earliest phases of mammalian adaptation to a microbiota, the epigenetic effects of maternal microbial metabolites and the resulting potential protection from metabolic disease or immunopathology. Conversely, there are profound effects of early life adaptation on the dynamics of microbial colonisation and the potential blooms and extinctions for the incoming microbiota: the project will define the different mechanisms involved. Campo scientifico medical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesbiological behavioural sciencesethologybiological interactionsnatural sciencesbiological sciencesgeneticsepigenetics Parole chiave Commensal microbiota early life neonate host-microbial mutualism metabolic and immunopathologic disease models Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2016-ADG - ERC Advanced Grant Invito a presentare proposte ERC-2016-ADG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante UNIVERSITAET BERN Contribution nette de l'UE € 2 500 000,00 Indirizzo HOCHSCHULSTRASSE 6 3012 Bern Svizzera Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Espace Mittelland Bern / Berne Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 500 000,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto UNIVERSITAET BERN Svizzera Contribution nette de l'UE € 2 500 000,00 Indirizzo HOCHSCHULSTRASSE 6 3012 Bern Mostra sulla mappa Regione Schweiz/Suisse/Svizzera Espace Mittelland Bern / Berne Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 500 000,00
