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Functional study of sox9 protein role in vertebrates sex determination and chondrogenic differentiation


Research objectives and content
In mammals, and probably in all vertebrates, the transcription factor SOX9 is developmentally bi-potential: it has a crucial role in chondrogenesis and a central involvement in testis determination. The SOX9 gene was cloned in 1994 as the gene responsible for a severe syndrome affecting cartilage formation (Compomelic Dysplasia) generally accompanied by sex reversal. In this project, by functional interactions study of SOX9 with other transcription factor, or in homomere complexes, I propose to investigate the molecular processes governing the SOX9 protein action in chondrogenic events or in sexual differentiation. This project has three fundamental components: - the cloning and the characterisation of genes involved in male sex determination and regulated by both SOX9 and SF1 (another transcription factor involved in sex determination which interact with SOX9). - the functional study of the physiological significance of SOX9 self-association and the implication of this homo dimer in
chondrogenic-specific gene regulation. - the research of interacting protein that could be involved in regulation of the transcriptional capacity of the SOX9 protein, or interact with SOX9 in a signal transduction pathway, by using SOX9 in a two hybrid screen. Training content (objective, benefit and expected impact)
Because I will apply for a research position in France for the study of the sex determination process, after six years of working on the SRY gene product, the initiating factor of testis determination, I am interested to complete my formation by the study of a major piece of the sex determination puzzle: the SOX9 protein. Gerd Scherer's group is to my knowledge one the best scientific environment to study this protein and its regulation: they have cloned the SOX9 gene in 1994 and were the first group to publish in 1996 the first data concerning the physiological function of the SOX9 protein. Using powerful tools such as the two hybrid screen and gene transactivation techniques, this laboratory will provide me with the opportunity to learn how to apply such technology to the SOX9 protein.
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Albert-Ludwigs-Universität Freiburg
79104 Freiburg

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