Objective 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. Fields of science natural sciencesbiological sciencessynthetic biologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutation Keywords genotype to phenotype map fitness landscape epistasis Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-COG - ERC Consolidator Grant Call for proposal ERC-2017-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA Net EU contribution € 1 998 280,00 Address Am campus 1 3400 Klosterneuburg Austria See on map Region Ostösterreich Niederösterreich Wiener Umland/Nordteil Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA Austria Net EU contribution € 1 998 280,00 Address Am campus 1 3400 Klosterneuburg See on map Region Ostösterreich Niederösterreich Wiener Umland/Nordteil Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
