Objective
Ion channel genes have long been linked to Mendelian focal epilepsies, but my recent finding of frequent mutations in DEPDC5 opens completely new perspectives. DEPDC5 is an inhibitor of the mTORC1 (mammalian target of rapamycin) signaling pathway, the master regulator of cell proliferation and growth. Mutations of this gene are found in a wide spectrum of focal epilepsy syndromes, with or without cortical malformations. I propose to examine the links between DEPDC5 and the mTORC1 pathway in cortical development and the genesis of epileptic activity.
My proposal work will combine high-throughput sequencing, in vivo proteomics, biochemistry, electrophysiology, and animal behavior testing (video-EEG). Functional analyses will be made on human postoperative tissue and neuronal cultures from human iPSC and specific rodent models. These approaches will enable me to (1) ask if and how the mTORC1 signaling pathway may contribute to epileptogenesis and seizures in patients with DEPDC5 mutations, (2) attempt to explain the diversity of phenotypes, in particular the presence of cortical lesion by searching for somatic brain mutations in the gene, (3) explore neurobiology pathways and partners of DEPDC5, and (4) identify novel actors for inherited focal epilepsies.
Our results will help us understand the genesis of epileptic networks, and more generally how defects in mTORC1 signaling cascade cause neurologic conditions. We anticipate genetic studies on germline and somatic mutations will have a significant clinical impact for genetic counseling and improved prognosis. The molecules and pathways that will be studied in this proposal differ completely from ion channels and receptors that have been so far associated with focal epilepsies. Thus I hope to provide a new orientation for the field, to identify novel genetic mechanisms and to provide an unbiased route to new molecular therapeutic targets.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences basic medicine neurology epilepsy
- natural sciences biological sciences genetics mutation
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
- natural sciences biological sciences biological behavioural sciences ethology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
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.
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.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2015-CoG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75654 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.