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Mechanisms of Regeneration Initiation

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.
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Host institution

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW

Address

Kloveniersburgwal 29 Het Trippenhuis
1011 Jv Amsterdam

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 307 544,21

Beneficiaries (2)

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KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW

Netherlands

EU Contribution

€ 1 307 544,21

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany

EU Contribution

€ 192 455,79

Project information

Grant agreement ID: 716894

Status

Ongoing project

  • Start date

    1 April 2017

  • End date

    31 March 2022

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 500 000

  • EU contribution

    € 1 500 000

Hosted by:

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW

Netherlands