Objectif I will study the role of the transcription factor Nfix, in post-natal skeletal muscle growth and regeneration, and in the pathogenesis of muscular dystrophies. I have recently demonstrated the role of the transcription factor Nuclear Factor IX, Nfix, in driving the transcriptional switch from embryonic to fetal myogenesis, characterized by a switch from slow to fast twitching and more mature fibers. Current data show that Nfix is also strongly expressed in satellite cells (SCs), the muscle adult stem cells responsible for post-natal muscle growth and regeneration. Therefore, I will investigate: 1. The gene expression profile of the muscle specific Nfix null SCs in vitro in comparison with wt SCs. 2. The ability of Nfix deficient SCs to repair muscle damage in comparison with wt SCs. Moreover, I will study the possible use of Nfix in muscular dystrophies. Muscular dystrophies are characterized by primary wasting of skeletal muscle and currently lack a therapy. Among the different approaches, many efforts are directed to induce hypertrophy in dystrophic to counteract progressive degeneration. This is achieved by enhancing regeneration at the expense of the satellite cell pool. Interestingly, fast muscle fibers are preferentially affected in different muscular dystrophies. As Nfix regulates slow myosin expression, I propose that a slower twitching muscle may escape muscle degeneration in a dystrophic mouse model. In this perspective, the possible interference of Nfix with the pathogenesis of muscular dystrophy will be studied by crossing muscle-specific Nfix null mice alpha sarcoglycan null mice ( a model for Limb Girdle 2D muscular dystrophy) (Aim 3). The results of this study will have important implications for the understanding of the mechanisms regulating post-natal muscle growth and regeneration and potentially as a novel therapy for muscular dystrophy. Champ scientifique medical and health sciencesbasic medicineneurologymuscular dystrophiesmedical and health sciencesmedical biotechnologycells technologiesstem cells Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Appel à propositions ERC-2011-StG_20101109 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil UNIVERSITA DEGLI STUDI DI MILANO Contribution de l’UE € 1 386 945,00 Adresse Via Festa Del Perdono 7 20122 Milano Italie Voir sur la carte Région Nord-Ovest Lombardia Milano Type d’activité Higher or Secondary Education Establishments Chercheur principal Graziella Messina (Dr.) Contact administratif Stefania Varotto (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITA DEGLI STUDI DI MILANO Italie Contribution de l’UE € 1 386 945,00 Adresse Via Festa Del Perdono 7 20122 Milano Voir sur la carte Région Nord-Ovest Lombardia Milano Type d’activité Higher or Secondary Education Establishments Chercheur principal Graziella Messina (Dr.) Contact administratif Stefania Varotto (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
