Objetivo "The applicant proposes a 2-year project to be performed under the supervision of Prof Bernheim, a neuromuscular disease expert at the University of Geneva. The goal of this project is to determine the role of isoforms of calcium-independent isoform phospholipase A2 (iPLA2) in cytosolic calcium entry and muscle cell death during Duchenne muscular dystrophy (DMD).DMD is the most severe case of muscle-wasting diseases of the muscular dystrophies family. It affects 1 in 3500 children, and is caused by mutations in dystrophin mRNA leading to the absence of the protein in skeletal muscles from affected patients. As dystrophin is an important player in muscle maintenance, its absence leads to skeletal muscle degeneration. To date, this is an incurable disease with 100% of fatality. Affected boys first lose the ability to walk, then breath, and finally die before being 30 years old. Although many mutations have been characterized, more research is needed to understand the molecular and signaling mechanisms underlying DMD, and increase the opportunities to find new therapeutic targets. Recent experiments have highlighted the importance of calcium entry in muscle fibers death. iPLA2 appears to have a role in this elevated cytosolic calcium, and has been shown to be upregulated both in DMD patients and dystrophic mdx mice. The applicant will 1) establish the implication and roles of the different iPLA2 isoforms in DMD by comparing calcium responses and muscle cell-death in wild-type (wt) and mdx muscle fibers, and 2) determine the effects of specific inhibitors on muscle cell survival.This project could have beneficial issues towards developing new strategies to counteract cytosolic calcium imbalance in muscle fibers from DMD patients, and thus potentially alleviate their symptoms.The applicant will benefit from the expertise of Prof Bernheim and the knowledge she previously acquired abroad to conduct this research project, and later pursue a research and teaching career in Europe." Ámbito científico engineering and technologymaterials engineeringfibersmedical and health sciencesbasic medicineneurologymuscular dystrophiesduchenne muscular dystrophynatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinemedical genetics Programa(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) FP7-PEOPLE-2010-IIF - Marie Curie Action: "International Incoming Fellowships" Convocatoria de propuestas FP7-PEOPLE-2010-IIF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IIF - International Incoming Fellowships (IIF) Coordinador UNIVERSITE DE GENEVE Aportación de la UE € 187 028,80 Dirección RUE DU GENERAL DUFOUR 24 1211 Geneve Suiza Ver en el mapa Región Schweiz/Suisse/Svizzera Région lémanique Genève Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Laurent Bernheim (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
