Objective
Evidence is emerging that rapid, profound and persisting changes in gene expression regulation and post-transcriptional regulation underlies the epileptogenic process. The current proposal builds on preliminary data which demonstrates that rapid reduction of a microRNA; miR-124, causes increased expression and activity of NRSF, a master-regulator of epileptogenesis. The current proposal will build on this and investigate other gene networks regulated by miR-124 in neurons, by developing the first miR-124 KO mouse using CRISPR technology and a miR-124 overexpressing mouse. These transgenic mice will then be profiled at the epigenomic level using ATAC-Seq, the transcriptome level using HITS-CLIP and ribosomal profiling and the proteomic level using mass spec. This will be the first study to examine the pleiotropic role of miR-124 in mature neurons and identify gene networks regulated by this neuronally enriched miRNA. If miR-124 disruption causes aberrant activity of epigenetic modifiers including NRSF then we will test whether miR-124 restitution can restore correct gene expression networks and prevent or modify epileptogenesis in a mouse model of the disorder. Next we will determine whether data obtained in mouse models is translatable to the human form of the condition by obtaining and maintaining resected human epileptic hippocampus live in culture. We will ectopically introduce miR-124 and test the effect of miR-124 restitution on network activity and energetics using live-calcium imaging as well as the epigenomic and transcriptomic effects. Together this proposal represents the most in-depth analysis of miRNA function and will set the standard for future functional analyses of these molecules. Furthermore it has the potential to intervene in disease process and apply findings to a relevant human model providing a novel therapeutic target for the treatment of epilepsy.
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.
- medical and health sciences basic medicine neurology epilepsy
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2015
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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.
D02 YN77 DUBLIN 2
Ireland
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.