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Mapping the axolotl brain and its regeneration

Project description

Multiscale characterisation of the axolotl brain and its regeneration

Axolotls are salamanders with the unique capacity for brain regeneration after major injury. Details regarding molecular mechanisms and the degree of circuit functionality and behavioural recovery are not known. The ERC-funded AxoBrain project aims to establish the axolotl as a model system for the study of central nervous system regeneration leading to innovative strategies for regenerating mammalian tissue. AxoBrain will map the brain cell types and connections at molecular, cellular and circuit levels. It will also establish protocols to study damage response and circuit regeneration mechanisms. Outcomes will leverage multiomics, behavioural assays and CRISPR perturbation among others.

Objective

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

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Keywords

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Programme(s)

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Topic(s)

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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.

HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2023-SyG

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Host institution

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
Net EU contribution

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.

€ 3 000 000,00
Address
DR BOHRGASSE 3
1030 WIEN
Austria

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Region
Ostösterreich Wien Wien
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

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.

€ 3 000 000,00

Beneficiaries (3)

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