Objective
Neurotransmission relies on the precise formation and maturation of synaptic vesicles (SVs), yet the early stages of their biogenesis remain poorly understood. Precursor vesicles (PVs) are the nascent carriers that transport SV and active zone proteins from the neuronal soma to presynaptic terminals, but their molecular composition, architecture, and formation mechanisms are unknown. Dysfunction in these processes is tightly linked to neurological disorders such as autism, epilepsy, and Parkinson's disease, highlighting both the fundamental and biomedical importance.
This project aims to establish the first comprehensive structural and molecular framework of PVs. Building on the researcher's expertise in structural analysis of synaptic proteins and the host laboratory's pioneering work in presynapse formation, the action will pursue three objectives: (1) define the architecture and composition of isolated PVs from human iPSC/ESC-derived neurons using cryogenic electron microscopy and tomography (cryo-EM and cryo-ET), and quantitative proteomics; (2) visualize PVs in situ within axons through advanced correlative light and electron microscopy to uncover cargo identity and transport mechanisms; and (3) resolve the origin, remodelling, and maturation of PVs into SVs using pulse-chase labelling strategies and gene engineering verification.
The methodology integrates structural biology, proteomics, and neuronal cell models to overcome the scarcity and transient nature of PVs. The anticipated outputs—structural atlases, proteomic datasets, and mechanistic models—will deliver unprecedented insight into presynaptic biogenesis. By resolving how PVs form, remodel, and mature into SVs, the project will close a major knowledge gap in neuroscience. The results will not only advance understanding of synaptic biology but also provide methodological innovations broadly applicable to cell biology and neuropharmacology, strengthening European leadership in neuro-structural research.
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
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences cell biology
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences biological sciences molecular biology structural biology
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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
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) HORIZON-MSCA-2025-PF
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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.
12489 Berlin
Germany
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.