Project description
Disrupted vesicles and brain development
Brain cells communicate by releasing signalling molecules stored in tiny membrane-bound compartments. A family of proteins called SNAREs controls this release by enabling these compartments to fuse with the cell membrane. Mutations in SNARE-encoding genes cause a group of neurodevelopmental disorders called SNAREopathies which are characterised by seizures, developmental delays, autism and speech impairments. With the support of the Marie Skłodowska-Curie Actions programme, the SNAREopathies project will investigate how SNARE mutations disrupt a critical developmental process called the GABA switch. This determines how the neurotransmitter GABA acts on neurons and is essential for forming balanced brain networks. Using patient cells and a novel high-throughput imaging platform, researchers will characterise this disruption and screen candidate compounds for restoring normal neuronal signalling.
Objective
SNARE proteins are essential for brain cell communication. They enable the release of signaling molecules like neurotransmitters and neuropeptides by facilitating the fusion of storage vesicles with the cell membrane. Mutations in genes coding for SNARE proteins cause a group of neurodevelopmental disorders known as SNAREopathies, which can include symptoms such as seizures, developmental delays, autism, and motor or speech impairments. SNAREopathies show very high phenotypic diversity even for patients carrying the same mutation, suggesting that other factors—like the patient's genetic background or other developmental processes—may influence the disease phenotype.
One critical process in the brain development is the “GABA-switch”, which determine the GABA neurotransmitter’s action on neurons; early in development, GABA excites neurons; later, it becomes inhibitory. This switch is vital for the brain to form stable and balanced networks, and it depends on precise control of chloride levels inside neurons. Disruption of this switch has been linked to disorders such as epilepsy and autism.
My project will use human neurons derived from stem cells carrying patient-specific SNARE variants to study how these variants affect the timing and function of the GABA-switch. I will develop a novel high-throughput, microscopy-based assay that simultaneously measures intracellular chloride concentration and neuronal network activity, allowing precise determination of the timing of the GABA-switch and its relationship to changes in neuronal activity. The functional analysis will be complemented by molecular profiling to uncover underlying mechanisms of affected molecular pathways in SNAREopathies. Finally, I will use my high-throughput microscopy platform to screen candidate compounds with the potential to restore proper signaling in affected neurons. This project will help to better understand SNAREopathies and lay the groundwork for new therapeutic strategies.
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 biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences genetics mutation
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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.
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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-2025-PF
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1165 KOBENHAVN
Denmark
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