Project description
Engineering axon regeneration
The brain’s neural circuits are built during development by axons navigating through precise chemical and physical guidance cues. After injury, these cues are lost, leaving regenerating axons without direction and preventing functional re-innervation in the central nervous system. Overcoming this limitation is a central challenge in regenerative neuroscience. The ERC-funded GAP project will explore a new way to actively guide neuronal axons during regeneration. Scientists will engineer neurons to trigger elongation or retraction and thereby precisely control their navigation. This will make it possible to steer axons in chosen directions and encourage reconnection in damaged networks. Project results will pave the way for novel therapies for paralysis after spinal cord injury.
Objective
Axon navigation is guided by spatial patterns of chemical and physical cues in the developing brain. After a damage, the pattern is lost. Axons do not have instructions to reach their target. Axon regeneration, if stimulated, occurs by chance. Unfortunately, current technologies do not allow us to control axon navigation decisions, and guided re-innervation is not possible in the central nervous system (CNS). The GAP project aims to fill this knowledge gap by modulating neuron mechanotransduction, in order to program axon pathfinding and to differentiate axon navigation decisions. Cells will be engineered to express magnetic nano-switches that can generate forces in specific nano/micro domains of specific neurons. Depending on the domain, the force triggers a different mechanotransduction pathway, resulting in axon elongation or axon retraction. The integration of the different outputs from different neurons can be used to re-shape the network.
GAP will demonstrate the ability: i) to change navigation decisions (e.g. to guide axon elongation in the direction of a repelling cue or to disengage axon outgrowth mediated by an attracting cue); ii) to differentiate between different navigation decisions in a mixed neuronal population (e.g. excitatory versus inhibitory neurons); iii) to control axon navigation decisions in a living organism (e.g. promoting reinnervation of excitatory neurons in models of spinal cord injury). GAP would demonstrate the ability to control neural network remodeling which remains an unmet challenge for science.
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.
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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)
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)
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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-ERC - HORIZON ERC Grants
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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) ERC-2024-ADG
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56126 PISA
Italy
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