Descripción del proyecto
Las moscas podrían proporcionar pistas sobre el papel de los cromosomas sexuales en el dimorfismo de la enfermedad
Todas las células de un organismo tienen todos los cromosomas de dicho organismo y la capacidad para producir todas las proteínas que este necesita. Incluso las células somáticas como las de los riñones o los intestinos cuentan con los cromosomas sexuales. Cada célula expresa solamente los genes que necesita para realizar su función y las células de los órganos sexuales lo hacen de una forma que modula las hormonas relacionadas con las diferencias sexuales. Sin embargo, no está claro la manera en que los cromosomas sexuales de otras células afectan al dimorfismo sexual y cómo se relaciona esto con la enfermedad. CellSex prevé averiguarlo mediante un amplio estudio de todo el cuerpo utilizando el modelo de la mosca Drosophila. Los estudios pioneros sobre deleción del cromosoma Y específica de los órganos deberían ofrecer una respuesta a las preguntas abiertas desde hace mucho tiempo acerca de la enfermedad y el sexo celular.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
75794 Paris
Francia