[METACAD] Mechanistic tracing of cadherin evolution in unicellular relatives of animals
Ente: EC
Scadenza: 2029-08-31
Importo max: 194.075 EUR
Paese: EU
Descrizione
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.
Settori: Horizon Europe Topics
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