Projektbeschreibung
Einfluss von Geschlechtschromosomen auf Geschlechtsdimorphismus bei Fruchtfliegen
Jede Zelle enthält jeweils alle Chromosomen eines Organismus, sodass sämtliche Proteine dieses Organismus hergestellt werden können. Zwar besitzen auch somatische Zellen (z. B. in Nieren oder Darm) Geschlechtschromosomen, aber jede Zelle exprimiert nur die für ihre jeweilige Aufgabe benötigten Gene. Zellen der Geschlechtsorgane modulieren Hormone so, dass geschlechtsspezifische Unterschiede entstehen. Wie Geschlechtschromosomen anderer Zellen auf den Geschlechtsdimorphismus wirken und in welchem Zusammenhang dies mit Krankheiten steht, ist allerdings noch unklar. Das Projekt CellSex konzipiert daher eine umfassende Ganzkörperanalyse des Modellorganismus Fruchtfliege (Drosophila). Bahnbrechende organspezifische Studien zur Deletion von Y-Chromosomen werden, so hofft man, Antworten auf lange offene Fragen zum zellulären Geschlecht und zu Krankheiten liefern.
Ziel
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.
Wissenschaftliches Gebiet
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-STG - Starting GrantGastgebende Einrichtung
75794 Paris
Frankreich