Objectif The fitness landscape, the representation of how the genotype manifests at the phenotypic (fitness) levels, may be among the most useful concepts in biology with impact on diverse fields, including quantitative genetics, emergence of pathogen resistance, synthetic biology and protein engineering. While progress in characterizing fitness landscapes has been made, three directions of research in the field remain virtually unexplored: the nature of the genotype to phenotype of standing variation (variation found in a natural population), the shape of the fitness landscape encompassing many genotypes and the modelling of complex genetic interactions in protein sequences. The current proposal is designed to advance the study of fitness landscapes in these three directions using large-scale genomic experiments and experimental data from a model protein and theoretical work. The study of the fitness landscape of standing variation is aimed at the resolution of an outstanding question in quantitative genetics: the extent to which epistasis, non-additive genetic interactions, is shaping the phenotype. The second aim of characterizing the global fitness landscape will give us an understanding of how evolution proceeds along long evolutionary timescales, which can be directly applied to protein engineering and synthetic biology for the design of novel phenotypes. Finally, the third aim of modelling complex interactions will improve our ability to predict phenotypes from genotypes, such as the prediction of human disease mutations. In summary, the proposed study presents an opportunity to provide a unifying understanding of how phenotypes are shaped through genetic interactions. The consolidation of our empirical and theoretical work on different scales of the genotype to phenotype relationship will provide empirical data and novel context for several fields of biology. Champ scientifique natural sciencesbiological sciencessynthetic biologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutation Mots‑clés genotype to phenotype map fitness landscape epistasis Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2017-COG - ERC Consolidator Grant Appel à propositions ERC-2017-COG Voir d’autres projets de cet appel Régime de financement ERC-COG - Consolidator Grant Institution d’accueil INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA Contribution nette de l'UE € 1 998 280,00 Adresse Am Campus 1 3400 Klosterneuburg Autriche Voir sur la carte Région Ostösterreich Niederösterreich Wiener Umland/Nordteil Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 998 280,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA Autriche Contribution nette de l'UE € 1 998 280,00 Adresse Am Campus 1 3400 Klosterneuburg Voir sur la carte Région Ostösterreich Niederösterreich Wiener Umland/Nordteil Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 998 280,00
