Project description
Modelling brain organoids to investigate focal cortical epilepsy
Mild Malformation of Cortical Development with oligodendroglial hyperplasia in Epilepsy (MOGHE) is a neurodevelopmental disorder caused by mutations in the SLC35A2 gene, leading to a loss of galactose in glycans. The only available treatment for related seizures is the surgical removal of the affected brain area. Supported by the Marie Skłodowska-Curie Actions programme, the EpiGlyco project will model MOGHE by creating SLC35A2 knockout myelinating organoids to investigate its genomic, histological, and transcriptomic features. The project will use imaging and electrophysiological techniques to assess traits like oligodendroglial hyperplasia and hypomyelination. High-throughput methods such as single-cell RNA sequencing and glycoproteomics will identify potential candidates and validate them with patient tissue samples.
Objective
An increasing number of neurodevelopmental pathologies are associated with disorders of glycosylation. One such disorder is MOGHE (Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy), which is primarily caused by brain somatic mutations in the gene SLC35A2. This gene encodes the sole known ER/Golgi UDP-galactose transporter, and mutations in SLC35A2 result in loss of galactose from glycans. The only therapeutic approach to control MOGHE-related seizures is surgical resection of the affected brain region. The host lab has used this tissue to gain insight into the genomic, histological and transcriptomic characteristics of MOGHE. To better understand the pathophysiology of this condition and promote future therapeutic approaches (e.g. galactose supplementation), I will model MOGHE by generating mosaic SLC35A2 knockout myelinating organoids. Through imaging and electrophysiological approaches, I will use these organoids to understand the development of the phenotypic characteristics of MOGHE: oligodendroglial hyperplasia, hypo-myelination, defective neuronal migration, and altered neuronal electrical activity. To better understand the mechanisms underpinning these phenotypes, I will use high-throughput approaches, including single-cell RNA sequencing and glycoproteomics to identify candidate conveyors. Findings from these experiments can then be validated on patient tissues available in the host laboratory. Beyond therapeutic perspectives, the mosaic nature of this model provides an unprecedented opportunity to gain insight into the cell autonomous and non-cell autonomous roles of glycans in cortical development and function. This project incorporates the state of the art in techniques used to study brain development and glycobiology and thus will expand on my existing skills as a researcher in a highly collaborative and open host environment and help me reach my goal of becoming an independent researcher.
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 basic medicine physiology pathophysiology
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- medical and health sciences basic medicine pathology
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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)
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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)
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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
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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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(opens in new window) HORIZON-MSCA-2024-PF-01
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75013 Paris
France
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