Cell proliferation, differentiation and death are controlled by different transcription factors amongst which the non-steroid nuclear receptors (nsNR). Deciphering the mechanisms of action of nsNR is a challenge in various research fields ranging from cancer and neurodegenerative disorders to metabolic diseases. According to the canonical signalling pathway liganded nsNR, in the form of dimers with a rexinoid receptor (RXR), bind to specific DNA response element of target genes and activate transcription.
Retinoic acid (RA) receptors (RARs) belong to the nsNR family. RA is the active metabolite of vitamin A, which is indispensable for normal embryonic development and, postnatally, for survival, growth, reproduction and epithelial differentiation. Its properties to induce cell differentiation are used to treat diseases, from benign defects to cancers. According to in vitro data, RARs can act via several non canonical signalling pathways independently of RXR. The InVivo_RA_NonCanon project proposes to characterize such pathways in vivo, using the seminiferous epithelium of the testis as a model system. Working hypotheses have been constructed which integrate yet unpublished data aimed at uncovering genes differentially expressed in RA-deficient contexts and existing datasets identifying RAR binding sites genome wide. The experimental strategy will combine in vitro experiments to identify the mechanisms of action of RARs and in vivo genetic analyses, in the mouse, to test their functionality in a physiological context.
Also, InVivo_RA_NonCanon aims at offering to a young scientist with an excellent scientific record, multi-disciplinary training and research experience in the field of cell biology with the goal of broadening the applicant’s skills in science on complementary subjects. The overall mission is to train the young researcher to become an independent scientist as well as to prepare him for a leading position in academia.