Objective How variations in whole chromosome number impact organism homeostasis remains an open question. Variations to the normal euploid genome content are frequently found in healthy animals and are thought to contribute with phenotypic variability in adverse situations. Yet they are also at the basis of several human diseases, including neuro-developmental disorders and cancer. Our preliminary data shows that physiological aneuploidy can be identified in certain cells during development. Moreover, we have observed that when induced through mutations, non-euploid cells are effectively eliminated from the cycling population. A quantitative view of the frequency of non-euploid karyotypes and the mechanisms underlying their genesis is lacking in the literature. Further, the tissue specific responses at play to eliminate non-euploid cells, when induced through mutations are not understood. The objectives of this proposal are to quantitatively assess the occurrence of physiological chromosome number variations gaining insight into mechanisms involved in generating it. Additionally, we will identify the tissue-specific pathways involved in maintaining organism homeostasis through the elimination of non-euploid cells. We will use a novel genetic approach to monitor individual chromosome loss at the level of the entire organism, combine it with quantitative methods and state-of-the art-microscopy, and focus on two model organisms - Drosophila and mouse - during development and adulthood. We predict that the findings resulting from this proposal will significantly impact the fields of cell, developmental and animal physiology, generating novel concepts that will bridge the existing gaps in the field, and expand our understanding of the links between karyotype variations, animal development and disease establishment. Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticschromosomesmedical and health sciencesbasic medicinephysiologyhomeostasis Keywords Aneuploidy polyploidy cell death premature differentiation stem cells epithelial cells tissue-dependent responses microcephaly cancer Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-COG - ERC Consolidator Grant Call for proposal ERC-2016-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution INSTITUT CURIE Net EU contribution € 1 400 276,02 Address RUE D ULM 26 75231 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations 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 Total cost € 2 000 000,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSTITUT CURIE France Net EU contribution € 1 400 276,02 Address RUE D ULM 26 75231 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations 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 Total cost € 2 000 000,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France Net EU contribution € 599 723,98 Address RUE MICHEL ANGE 3 75794 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations 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 Total cost € 599 723,98
