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Mechanisms of Regeneration Initiation

Objective

Injury poses a key threat to all multicellular organisms. However, while some animals can fully restore lost body parts, others can only prevent further damage by mere wound healing. Which molecular mechanisms determine whether regeneration is induced or not is an unsettled fundamental question. I will use whole body regeneration, one of the most fascinating biological processes, as an experimental paradigm to identify the mechanisms of regeneration initiation. As a model organism I will employ planarians, flatworms with extraordinary plasticity that regenerate every piece of their body within a few days. I will mechanistically dissect how these animals rapidly induce an efficient regeneration program in response to tissue loss and define the key switches that determine whether a wound regenerates. Combining the astonishing regenerative abilities of planarians with new technologies I will first comprehensively describe the molecular changes occurring during the amputation response. Second, with a powerful novel assay developed in my lab - dormant fragments - that allows for the first time the separation of wounding from tissue loss in a single planarian, I will analyze the dynamics of the earliest regenerative events. Third, I will functionally characterize the regeneration-initiating signals and their target pathways combining in vivo RNAi and phenotypic assays. Fourth, with a regeneration-deficient planarian species, I will test whether the identified key regulators act as network nodes that can be utilized to rescue regeneration. Importantly, using vertebrate paradigms, such as the regenerating zebrafish fin, I will investigate conserved roles of these network nodes and validate general principles of regeneration initiation. This project will not only uncover conserved mechanisms of regeneration initiation but will also identify the switches that must be levered to induce regeneration in non-regenerating animals.

Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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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-2016-STG

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Host institution

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
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.

€ 1 307 544,21
Address
KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
1011 JV AMSTERDAM
Netherlands

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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.

€ 1 307 544,21

Beneficiaries (2)

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