Description du sujet de thèse

Sex determination is the process by which the bipotential gonad differentiates into either a testis in XY embryos or an ovary in XX embryos. This process not only initiates the sexual development of the individual but also influences adult physiology and the progression of many diseases. In 1990, the testis-determining gene was identified as SRY. More recently, our team identified the ovarian-determining factor as an alternatively spliced variant of WT1. However, the mechanism driving the production of this splice variant remains unknown. Recently, we identified a novel gene that is essential for sex determination, as its absence results in a failure of gonadal sexual differentiation. This discovery revealed a previously unrecognized regulatory layer in sex determination: post-transcriptional regulation.
Our current objective is to elucidate the mechanisms underlying this regulation and determine how it affects the expression of key genes involved in gonadal sex differentiation, including the sex determinants. Using genetic models, high-resolution microscopy, advanced transcriptomic tools, and biochemical analyses, we aim to uncover how specific candidate factors contribute to the alternative splicing of WT1, leading to the production of the ovarian determinant. We will also examine mRNA chemical modifications, structural dynamics, and stability in mutant versus control gonads. This research will deepen our understanding of the regulatory mechanisms governing sex determination and may pave the way for new diagnostic tools for the more than 40% of individuals with unexplained disorders of gonadal development.
We are looking for a highly motivated candidate with a master's degree in biology or biomedical sciences, and an excellent academic record. Good communication skills in English and strong interpersonal abilities are essential. Knowledge of developmental biology and mouse genetics would be an advantage. Applicants should provide the names and contact details of two academic referees.

Contexte de travail

The Institut de Biologie Valrose (iBV) is a centre of excellence funded by the CNRS, Inserm and the Université Côte d'Azur (Nice). The iBV's mission is to study the fundamental principles governing the development of organisms and to identify the molecular basis of diseases, including cancer. You will have access to cutting-edge technological platforms, including microscopy, cytometry, histology and bioinformatics infrastructures, as well as animal facilities for various model organisms.
The Chaboissier team is interested in sex determination and uses genetics to study the mechanisms of gonadal sex development and their links to diseases.

Contraintes et risques

There are no specific constraints.