AxoMatrx | How do dynamic changes extracellular matrix guide regenerative events in Axolotl?

Summary
How do dynamic changes of the extracellular matrix guide regenerative events in Axolotl?

To what extent the dedifferentiation of mature cells is an intrinsic property of the cells or a product of interaction with the microenvironment is an exigent question in the regeneration field.
In this project I will assess what initiates the regenerative response with an emphasis on deciphering what components are important for formation of the blastemal stem cell niche. Specifically, I will address whether ECM actively regulates the limb regenerative response or is merely a bystander. Although the importance of MMPs and ECM components in limb regeneration has been reported several times, few attempted to understand the role of ECM as signaling hub rather than as a “passive wall”.

To address this, I will use tools developed in the Tanaka lab and combine those with my ECM expertise. I will characterize active ECM components during several distinct stages of limb regeneration to create an ECM “atlas” depicting extracellular changes during healing. I will use the obtained dataset to identify proteins which are important for the regenerative response by depleting these factors during axolotl regeneration and by testing their ability to induce ectopic limb growth using the Accessory Limb Model. Lastly, I will attempt to translate the axolotl findings to the mammalian setting and facilitate regeneration in a non-regenerating context.
Surprisingly to date, no systemic characterization of extracellular molecules has been reported in regenerative systems, nor was any axolotl regenerative cue yet successfully translated to mammals. Thus, this characterization and candidate identification have far-reaching implications for both development and regenerative biology.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101015478
Start date: 01-09-2022
End date: 31-08-2024
Total budget - Public funding: 186 167,04 Euro - 186 167,00 Euro
Cordis data

Original description

How do dynamic changes of the extracellular matrix guide regenerative events in Axolotl?

To what extent the dedifferentiation of mature cells is an intrinsic property of the cells or a product of interaction with the microenvironment is an exigent question in the regeneration field.
In this project I will assess what initiates the regenerative response with an emphasis on deciphering what components are important for formation of the blastemal stem cell niche. Specifically, I will address whether ECM actively regulates the limb regenerative response or is merely a bystander. Although the importance of MMPs and ECM components in limb regeneration has been reported several times, few attempted to understand the role of ECM as signaling hub rather than as a “passive wall”.

To address this, I will use tools developed in the Tanaka lab and combine those with my ECM expertise. I will characterize active ECM components during several distinct stages of limb regeneration to create an ECM “atlas” depicting extracellular changes during healing. I will use the obtained dataset to identify proteins which are important for the regenerative response by depleting these factors during axolotl regeneration and by testing their ability to induce ectopic limb growth using the Accessory Limb Model. Lastly, I will attempt to translate the axolotl findings to the mammalian setting and facilitate regeneration in a non-regenerating context.
Surprisingly to date, no systemic characterization of extracellular molecules has been reported in regenerative systems, nor was any axolotl regenerative cue yet successfully translated to mammals. Thus, this characterization and candidate identification have far-reaching implications for both development and regenerative biology.

Status

SIGNED

Call topic

MSCA-IF-2020

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2020
MSCA-IF-2020 Individual Fellowships