Study of the molecular mechanisms that regulate SCN5A expression

Objective

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.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

• medical and health sciences clinical medicine cardiology cardiovascular diseases cardiac arrhythmia
• social sciences sociology demography mortality
• natural sciences biological sciences genetics DNA
• natural sciences chemical sciences inorganic chemistry alkali metals

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2010-RG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IRG - International Re-integration Grants (IRG)

Coordinator