Project description
Boosting nervous system repair and regeneration in mammals
The mammalian central nervous system (CNS) is an intricate and fragile structure that has a limited capacity to self-repair after injury. Neural stem cells in the mammalian CNS lack the gene regulatory circuits that dictate when and where to activate developmental gene expression for regeneration. Consequently, most of the cells lost to injury are never replaced. The ERC-funded EnhanceRegen project will carry out research to uncover the basic principles of gene regulation after CNS injury. Relying on advanced technologies, researchers will identify injury-responsive elements in the spinal cords of mice. Machine learning will aid them in decoding the rules of injury-sensing DNA elements. This will open new avenues for the design of smart gene therapies using synthetic regeneration enhancers.
Objective
The mammalian central nervous system (CNS) is the epitome of complex cellular architecture. Still, it has a limited capacity to self-repair after an injury, which contrasts with the regenerative potential of the CNS in lower vertebrates. Regeneration unfolds by the orchestrated triggering of developmental gene expression programs after injury. These programs are under the control of dedicated regeneration enhancer elements, which grant adult cells transcriptional access to developmental genes. Neural stem cells in the mammalian CNS lack the gene regulatory circuits that dictate when and where to activate the expression of developmental genes for regeneration. Consequently, most of the cells lost to injury are never replaced.
This proposal aims to rewire mammalian gene expression circuits to endow neural stem cells with the capacity to activate regenerative responses after injury.
First, building on innovative technologies, some of which that I developed, we will identify injury-responsive enhancer elements in the mouse spinal cord with single cell and spatiotemporal resolution. Then, using machine learning, we will decode the rules of injury-sensing DNA elements to design synthetic injury-responsive enhancers for precise gene expression control in neural stem cells. Finally, we will use synthetic enhancers in therapeutically relevant gene delivery systems to rewire gene circuits in order to promote the recruitment resident stem cells for cell replacement through the reactivation of developmental genes that would otherwise remain silent.
The proposed research will uncover basic principles of gene regulation after CNS injury and open new avenues for the design of smart gene therapies for regenerative medicine using synthetic regeneration enhancers.
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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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-STG
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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.
171 77 STOCKHOLM
Sweden
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.