Objective The complexity by which genotypes modulate phenotypic variation has been a major obstacle in understanding the basis of inter-individual differences. In the particular case of disease susceptibility, enormous efforts have been conducted among large consortia of quantitative geneticists, and a recent wealth of results showed both victories and frustrations. Victories because many genetic factors could successfully be linked to diabetes, heart failure, cancer, infectivity, and many other common diseases. Frustrations as it is becoming more and more apparent that genetic dissections are far from completion, with many unsolved questions especially regarding gene x environment interactions and incomplete penetrance. In this context, I propose to revisit the molecular basis of phenotypic diversity by addressing fundamental questions in a simple and powerful model organism: the yeast S. cerevisiae.Combining experimental biology and bioinformatics into a ‘systems’ approach, I propose 1) To reconsider our current view of genetic determinism. By examining the effect of genetic variation on single-cells, we will visualise how they shape probability laws underlying phenotypic outcomes. This will prepare us to the upcoming era of generalized single-cell analysis. 2) To investigate how chromatin epigenotypes affect phenotypic variations. We will characterize nucleosomal epi-polymorphisms and study their impact on transcriptional and phenotypic responses to environmental changes. This will establish whether and how individual epigenomes should be considered when planning trait dissections.This ambitious project is grounded on solid preliminary results and can be achieved thanks to my dual expertise in numerical science and experimental genetics. The questions addressed are fundamental for our understanding of living systems and the innovative methodology will help us integrate upcoming technologies into the construction of personalized medicine. Fields of science natural sciencesbiological sciencesgeneticsmedical and health sciencesclinical medicineendocrinologydiabetesmedical and health scienceshealth sciencespersonalized medicinemedical and health sciencesclinical medicinecardiologysocial scienceslaw Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS EU contribution € 1 499 660,00 Address RUE MICHEL ANGE 3 75794 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Pascaline Toutois (Dr.) Principal investigator Gael Yvert (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France EU contribution € 1 499 660,00 Address RUE MICHEL ANGE 3 75794 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Pascaline Toutois (Dr.) Principal investigator Gael Yvert (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
