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Mechanistic tracing of cadherin evolution in unicellular relatives of animals

Project description

Evolution of cell adhesion

The transition from unicellular organisms to complex multicellular animals is one of the most profound events in evolutionary history. Although many genes essential for multicellularity were already present in unicellular ancestors, it remains unclear how they were modified to assist in the formation of organised tissues. With the support of the Marie Skłodowska-Curie Actions programme, the METACAD project aims to investigate the evolutionary origins of cadherin-based cell adhesion. This system is central to tissue organisation, contact inhibition, and embryonic development in animals. By combining bioinformatics, structural biology, and functional genetics, researchers will reconstruct how primitive cell contacts evolved into the robust adhesion machinery that underlies animal tissue integrity. Project results could provide the first experimental evidence for this fundamental evolutionary transition.

Objective

A key insight about the origin of multicellular animals is that many genes critical for multicellularity were already present in their unicellular ancestors. Yet how these genes were modified and co-opted for true multicellularity remains unclear. This project will tackle the evolution of cell adhesion during the unicellular-to-multicellular transition, focusing on cadherins, which mediate stable adhesion, contact inhibition, and tissue organization in animals. I aim to reconstruct how cadherin-based adhesion first evolved in animals and was later co-opted to build organized tissues. Unicellular relatives of animals encode diverse cadherin-like proteins that often lack canonical cytoplasmic motifs for β-catenin binding, suggesting they may have functioned without stable cytoskeletal coupling. In these species, stage-specific expression of cadherins during aggregation and rosette formation suggests that ancestral cadherins may have enabled transient clustering and primitive contact signaling before true multicellularity emerged. I will test whether these ancestral adhesion systems laid the foundation for stable, cytoskeleton-coupled junctions in animals. I will combine three complementary approaches: 1) a bioinformatics survey of cadherin diversity and domain evolution; 2) a biochemical reconstitution and structural analysis to test homophilic adhesion and map binding interfaces; and 3) functional genetics experiments in unicellular holozoans to reveal cadherin roles and identify potential partners through interactome mapping. This project will provide the first experimental evidence for how primitive cell contacts evolved into the robust adhesion modules that shape animal growth and tissue integrity. Beyond cadherins, this work will create a framework for reconstructing ancestral protein functions that remain hypothetical in other systems.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution

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€ 194 074,56
Address
CALLE SERRANO 117
28006 Madrid
Spain

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Comunidad de Madrid Comunidad de Madrid Madrid
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Research Organisations
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