Descrizione del progetto
Le mosche potrebbero fornire indizi sul ruolo dei cromosomi sessuali nel dimorfismo delle malattie
Tutte le cellule di un organismo hanno tutti i cromosomi dell’organismo e la capacità di produrre tutte le proteine di cui l’organismo ha bisogno. Anche cellule somatiche quali quelle nei reni o nell’intestino hanno i cromosomi sessuali. Ogni cellula esprime solo i geni di cui ha bisogno per fare il suo lavoro, mentre le cellule degli organi sessuali lo fanno in un modo che modula ormoni legati alle differenze sessuali. Tuttavia, non è chiaro in quale modo i cromosomi sessuali in altre cellule influenzino il dimorfismo sessuale e in che modo questo si correla a una malattia. CellSex prevede di scoprirlo attraverso uno studio completo su tutto il corpo del modello di moscerino Drosophila. Studi pionieristici di delezione del cromosoma Y specifici per organo dovrebbero fornire risposte alle domande aperte su sesso cellulare e malattie.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
75794 Paris
Francia