Objective
Myelinated axons propagate action potentials across otherwise unsurmountable distances. The overarching hypothesis of the cryoNERVE project is that membrane morphology crucially determines axonal health and function. Mutations in genes coding for membrane-shaping proteins are the major cause of familial axonopathies like hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth (CMT) disease. However, current techniques lack the resolution to ascertain the functions of these proteins and their pathological dysfunction within native nerves. At the same time, the highly specialized architecture of axons and their delicate interplay with glia can only be studied in situ.
I have shown how cryo-electron tomography (cryo-ET) reveals the structural basis of neuronal function and disease within intact cells. However, cryo-ET imaging of tissues remains a major challenge. In cryoNERVE, we will develop cryo-ET workflows to image native nerve tissue at unprecedented resolution. We will build on these advances to study the function of HSP and CMT proteins within truly physiological environments. Specifically, we will investigate (i) how these proteins shape axonal organelles and their cross-talk, (ii) the mechanisms allowing myelin sheath formation and neuron-glia communication, and (iii) the alterations introduced by axonopathy-causing mutants.
Lastly, we will pioneer the first cryo-ET analyses of vitrified human tissues. Frustratingly, peripheral nerve biopsies from axonopathy patients often cannot be diagnosed with existing methods. We will examine patient biopsies at molecular resolution, and capitalize on our findings in flies and mice to reveal hitherto obscured pathological abnormalities. Thus, cryoNERVE will provide a holistic molecular and structural basis of human axonopathies like HSP and CMT, pave the way for high-resolution analyses of native human tissues and explore the potential of cryo-ET as a diagnostic tool with nanometric precision.
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
- natural sciences physical sciences optics microscopy electron microscopy
- 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.1.1 - European Research Council (ERC)
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-ERC - HORIZON ERC Grants
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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) ERC-2022-COG
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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.
37075 Goettingen
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.