Objective
Epilepsy, a global neurological disorder affecting around 70 million people, poses a significant medical challenge, with one-third of patients facing drug-resistant epilepsy. Cortical malformations such as focal cortical dysplasia type II (FCDII) are associated with pediatric drug-resistant epilepsy for which surgical intervention serves as the main therapeutic approach for seizure control. FCDII is marked by cortical dyslamination and the presence of abnormal cytomegalic cells. Recent findings show that FCDII results from brain mosaicism due to postzygotic mutations in genes of the mTOR pathway, which produces excessive activation of the pathway. Nevertheless, as the human surgical FCDII samples represent an advanced disease stage, we poorly understand its developmental origin and mechanisms. Moreover, the link between mTOR activation and epileptogenesis remains unclear.
To address these critical knowledge gaps, a disease-relevant FCDII model is needed. For the preservation of human-specific features, I will use a mosaic cortical organoid model that expresses an inducible MTOR-S2215F mutant construct to reflect the somatic nature of FCDII. Induction of the mutation at different time points will shed light on the specific time frame during which mutations occur in FCDII patients and enable us to generate a preclinical model replicating an FCDII-like phenotype. Next, I will perform single-cell transcriptomic profiling at various developmental stages to uncover the cellular and molecular mechanisms behind FCDII development. Finally, the neuronal network activity of mosaic FCDII cortical organoids will be characterized, focusing on identifying the primary drivers of epileptiform activity among mutant cytomegalic or non-mutant nearby cells. In brief, this preclinical FCDII model has the potential to unveil novel developmental mechanisms, offer new non-invasive avenues for treating FCDII patients with drug-resistant epilepsy, and boost my career trajectory in the field.
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
- medical and health sciences clinical medicine surgery surgical procedures
- natural sciences biological sciences genetics mutation
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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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.
75013 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.