Objectif Sudden cardiac death syndromes are an important cause of mortality in young individuals in developed countries. The SCN5A gene, which encodes the alpha subunit of the cardiac sodium channel, plays a key role in controlling the sodium currents during the action potential. When malfunctioning due to loss-of-function genetic defects, SCN5A may be responsible for lethal diseases like Brugada syndrome or familial conduction disease. However, little is known regarding SCN5A gene expression regulation, both at the transcriptional or posttranscriptional level. In this project I am proposing to further elucidate the molecular mechanisms that regulate the expression of the SCN5A gene. Using in vitro, cell culture and in vivo experimental approaches, I propose to study the following objectives: 1) To characterize the transcription factors implicated in the transcriptional regulation of the SCN5A promoter in cell culture, EMSA and ChIP experiments; 2) To study the role of DNA methylation in SCN5A expression by analyzing the presence of methylated DNA in cardiac cell derived genomic samples from a cohort of individuals; 3) To study the role of microRNAs with putative binding sites at the 3’UTR of the regulatory region of SCN5A to the cardiac sodium channel. We anticipate that these studies will bring new insights and better understanding of promoter regulation and sodium channel expression. Because of the clinical relevance of this cardiac channel in many arrhythmias, we predict that these studies will have an impact for the future diagnosis and treatment of patients with cardiac arrhythmias and sudden cardiac death syndromes. Champ scientifique medical and health sciencesclinical medicinecardiologycardiovascular diseasescardiac arrhythmiasocial sciencessociologydemographymortalitynatural sciencesbiological sciencesgeneticsDNAnatural scienceschemical sciencesinorganic chemistryalkali metals Programme(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) Thème(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Appel à propositions FP7-PEOPLE-2010-RG Voir d’autres projets de cet appel Régime de financement MC-IRG - International Re-integration Grants (IRG) Coordinateur UNIVERSITAT DE GIRONA Contribution de l’UE € 100 000,00 Adresse PLACA SANT DOMENEC 3 17004 Girona Espagne Voir sur la carte Région Este Cataluña Girona Type d’activité Higher or Secondary Education Establishments Contact administratif Montserrat Estopà Bagot (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
