Project description
From glial cell to neuron: reprogramming via transcription factors
Until a couple decades ago, scientists believed glial cells, including astrocytes, did not serve any function other than structural, acting like a ‘glue’ that holds the neurons together. We now know this heterogeneous population of cells plays important roles in modulating nervous system function, its development and in protecting it or aiding in recovery. Recently, the discovery that endogenous glial cells can be reprogrammed into functional neurons has offered new hope for recovery of neuronal loss after injury or disease. With the support of the Marie Skłodowska-Curie Actions programme, the CELLIDRECUT project will investigate the potential of so-called Onecut transcription factors to reprogramme in vivo astrocytes into functional neurons.
Objective
Neuronal loss is at the core of cognitive and functional failures of both acute brain injuries and neurodegenerative diseases. Direct neuronal reprogramming of local glial cells is emerging as a promising approach for restorative brain therapy. However, in order to use direct glia-to-neuron reprogramming for the treatment of neuronal loss we still need to address a number of challenges, namely reliable and long-term conversion into the desired neuron subtype. In this proposal we aim to generate specific neuronal subtypes using novel fate determinants in glia-to-neuron reprogramming, and to provide a detailed molecular analysis of the newly generated neurons over time. Our data indicate that ONECUT factors may represent excellent novel candidates for astrocyte reprogramming into neuronal fates. To address this possibility, in this proposal we will focus on the thalamocortical system, which represents the main input to the neocortex and it is essential to cortical processing. We hypothesize that the innovative combination of nuclei specific thalamic factors with ONECUT factors could reveal new avenues for the direct reprogramming of astrocytes into thalamic neurons of specific sensory modalities and may inform future strategies for brain repair. Here, we have unique expertise and molecular tools at hand that will allow us to reprogram astrocytes into specific neuron types in vitro and in vivo. Moreover, as our ultimate goal is to reprogram astrocytes to recover neuronal loss, we will test whether astrocytes from a sensory deprived thalamus can be reprogrammed. By using state-of-the-art techniques such as 3D light-sheet microscopy, calcium imaging and transcriptomic analysis, we will determine the fidelity and functionality of the newly generated neurons. This approach will offer us unparalleled advantages for the discovery of novel reprogramming combinations and address important questions about reliable and long-term conversion into the desired neuron type.
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 chemical sciences inorganic chemistry alkaline earth metals
- natural sciences physical sciences optics microscopy
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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)
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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.
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-2021-PF-01
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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.
28006 MADRID
Spain
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.