Description du sujet de thèse

Sex reversal in humans is a rare condition associated with infertility, and its molecular mechanisms are still unclear. While most cases of 46, XX male individuals are associated with SRY gene translocations onto the X chromosome (SRY being the gene that determines the formation of the testis, normally present on the Y chromosome), there are cases that are SRY-negative and instead involve duplications of the X-linked gene SOX3. We aim to elucidate the molecular mechanisms underlying SOX3-linked male reversal. Using innovative genomic engineering technologies, we will generate SOX3 duplications in new cell differentiation systems of human and mouse gonadal development, and study their impact using transcriptomic and chromosome conformation capture approaches. Genomic manipulations of Sox3 will also be tested in mutant mouse embryos to assess sex reversal in vivo. Understanding SOX3-driven sex reversal will help advancing diagnosis, clinical management, and fertility interventions.

Contexte de travail

The successful candidate will work in the context of the ERC-funded REGULADOSIX project in the “Developmental Regulation of Gene Dosage” team led by Rafael Galupa, within the MCD unit (UMR5077), at the Centre de Biologie Intégrative (CBI, Toulouse). The team works on understanding the regulation of gene dosage in the context of the mammalian X chromosome. The person recruited will be supervised by the team leader.

Contraintes et risques

- chemical hazards
- risks related to biological agents
- risk related to work equipment
- risks associated with working alone
- risks related to working on screens

Informations complémentaires

This PhD project is part of the REGULADOSIX project, funded by an ERC Starting Grant awarded to Rafael Galupa.