Summary
The Axolotl is an extraordinary model system to study regeneration in tetrapods. Remarkably, the axolotl is
able to regenerate parts of the brain after major injury, however the molecular mechanisms that orchestrate
regeneration are unclear, and the completeness of functional circuit and behavioral recovery is unknown. Our
vision is to develop the axolotl model system to rigorously study central nervous system regeneration, and
use discoveries from the axolotl to design novel strategies for regenerating mammalian tissues. The mapping
of brain cell types and connections in the axolotl will also have a profound impact on the understanding of
vertebrate brain organization and evolution.
In AxoBrain, we will integrate scale-crossing technologies to map the axolotl brain at molecular, cellular
and circuit resolution, and establish assays to understand how brain cells respond to damage and behavioral
circuits regenerate. Our project will be achieved through the following objectives: 1) We will generate a
spatiotemporal multiomic atlas of the axolotl brain at single cell resolution. 2) We will generate a
connectome of the axolotl retino-tectal-hindbrain circuit and develop behavioral and circuit functional assays
in response to visual stimulation. 3) We will establish injury assays and assess regeneration through
behavioral, connectomic and single-cell multiomic analysis. 4) Finally, we will apply CRISPR perturbation
screens with single-cell genomic readout in vivo and in vitro to identify modulators of regeneration.
AxoBrain utilizes quantitative and state-of-the-art methods to explore how the axolotl can regenerate neural
circuitry after injury. We have assembled a team with synergistic skill sets that will be required to achieve
our vision. This project is a groundbreaking starting point to rigorously investigate how mammals have lost
regeneration capabilities over evolution, and will serve as a springboard to design novel strategies for
regenerating
able to regenerate parts of the brain after major injury, however the molecular mechanisms that orchestrate
regeneration are unclear, and the completeness of functional circuit and behavioral recovery is unknown. Our
vision is to develop the axolotl model system to rigorously study central nervous system regeneration, and
use discoveries from the axolotl to design novel strategies for regenerating mammalian tissues. The mapping
of brain cell types and connections in the axolotl will also have a profound impact on the understanding of
vertebrate brain organization and evolution.
In AxoBrain, we will integrate scale-crossing technologies to map the axolotl brain at molecular, cellular
and circuit resolution, and establish assays to understand how brain cells respond to damage and behavioral
circuits regenerate. Our project will be achieved through the following objectives: 1) We will generate a
spatiotemporal multiomic atlas of the axolotl brain at single cell resolution. 2) We will generate a
connectome of the axolotl retino-tectal-hindbrain circuit and develop behavioral and circuit functional assays
in response to visual stimulation. 3) We will establish injury assays and assess regeneration through
behavioral, connectomic and single-cell multiomic analysis. 4) Finally, we will apply CRISPR perturbation
screens with single-cell genomic readout in vivo and in vitro to identify modulators of regeneration.
AxoBrain utilizes quantitative and state-of-the-art methods to explore how the axolotl can regenerate neural
circuitry after injury. We have assembled a team with synergistic skill sets that will be required to achieve
our vision. This project is a groundbreaking starting point to rigorously investigate how mammals have lost
regeneration capabilities over evolution, and will serve as a springboard to design novel strategies for
regenerating
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101118739 |
| Start date: | 01-04-2024 |
| End date: | 31-03-2030 |
| Total budget - Public funding: | 8 940 901,00 Euro - 8 940 901,00 Euro |
Cordis data
Original description
The Axolotl is an extraordinary model system to study regeneration in tetrapods. Remarkably, the axolotl isable to regenerate parts of the brain after major injury, however the molecular mechanisms that orchestrate
regeneration are unclear, and the completeness of functional circuit and behavioral recovery is unknown. Our
vision is to develop the axolotl model system to rigorously study central nervous system regeneration, and
use discoveries from the axolotl to design novel strategies for regenerating mammalian tissues. The mapping
of brain cell types and connections in the axolotl will also have a profound impact on the understanding of
vertebrate brain organization and evolution.
In AxoBrain, we will integrate scale-crossing technologies to map the axolotl brain at molecular, cellular
and circuit resolution, and establish assays to understand how brain cells respond to damage and behavioral
circuits regenerate. Our project will be achieved through the following objectives: 1) We will generate a
spatiotemporal multiomic atlas of the axolotl brain at single cell resolution. 2) We will generate a
connectome of the axolotl retino-tectal-hindbrain circuit and develop behavioral and circuit functional assays
in response to visual stimulation. 3) We will establish injury assays and assess regeneration through
behavioral, connectomic and single-cell multiomic analysis. 4) Finally, we will apply CRISPR perturbation
screens with single-cell genomic readout in vivo and in vitro to identify modulators of regeneration.
AxoBrain utilizes quantitative and state-of-the-art methods to explore how the axolotl can regenerate neural
circuitry after injury. We have assembled a team with synergistic skill sets that will be required to achieve
our vision. This project is a groundbreaking starting point to rigorously investigate how mammals have lost
regeneration capabilities over evolution, and will serve as a springboard to design novel strategies for
regenerating
Status
SIGNEDCall topic
ERC-2023-SyGUpdate Date
17-11-2024
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