Description du projet
Les mouches pourraient fournir des indices sur le rôle des chromosomes sexuels dans le dimorphisme de la maladie
Toutes les cellules d’un organisme ont tous les chromosomes de l’organisme et la capacité de produire toutes les protéines dont l’organisme a besoin. Même les cellules somatiques comme celles des reins ou des intestins ont les chromosomes sexuels. Chaque cellule exprime uniquement les gènes dont elle a besoin pour faire son travail, et les cellules des organes sexuels le font d’une manière qui module les hormones liées aux différences sexuelles. Toutefois, il est difficile de déterminer la façon dont les chromosomes sexuels dans d’autres cellules affectent le dimorphisme sexuel et son lien avec la maladie. CellSex prévoit de la découvrir grâce à une étude complète à l’échelle de l’organisme de la drosophile. Des études pionnières sur la suppression des chromosomes Y spécifiques à un organe devraient fournir des réponses aux questions ouvertes depuis longtemps sur la maladie et les cellules sexuelles.
Objectif
The difference between males and females constitutes the largest phenotypic dimorphism in most species. In humans, this variation accounts for differences seen in the risk, incidence and response to treatment for a plethora of diseases; and much of these striking differences are not explained at this time. While sex organ-derived hormones play key roles in sculpting and maintaining sex differences, my recent work highlighted the importance of cell-intrinsic mechanisms involving the sex chromosomes. In fact, using fly models I demonstrated that the sex of intestinal stem cells plays a key role in the adult gut, both for the organ size and for the sex-specific pre-disposition to tumours. While these findings establish the proof-of-principle of the influence of sex chromosomes in adult cells, essential gaps remain to be filled. Indeed, the full range of phenotypic consequences of the presence of sex chromosomes in somatic cells, the genes, the mechanisms involved and their sites of action remain entirely elusive. My research proposal aims to understand how cellular sex impacts physiology across the body using Drosophila as an in vivo model. This question has been poorly investigated in part due to the difficulties of studying sex chromosome effects. Flies will offer the remarkable possibility of generating mosaic animals in which sex chromosomes will be genetically manipulated in defined organs.
Here I will combine classical fly genetics, novel genetic methods and cutting-edge genomic techniques to: 1. characterise new cellular sex pathways driving sex differences in body size and in behaviours, 2. study the role of sex determinant coding changes in sex trait evolution, 3. achieve, for the first time, organ-specific Y chromosome deletion, and use this new method to study how the Y chromosome controls sex gap in longevity.
Thus, results from this research should have major impact on our understanding of the importance of cellular sex in physiology and disease.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
75794 Paris
France