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Molecular sociology and functional compartmentalization of the archaeal relatives of eukaryotes

Objective

Eukaryotes originate from an endosymbiotic merger between the mitochondrial ancestor and an Asgard archaeon, but the topology of this interaction remains unclear. Intriguingly, first analyses of the ultrastructure of Asgard archaea uncovered eukaryotic hallmark features, such as an actin and microtubule cytoskeleton, as well as a unique morphology with extended protrusions connected to genome-containing cell bodies.
I hypothesize that - despite the lack of membrane-bound compartments - the complex cell plan of Asgard archaea is functionally compartmentalized. ARCHAEAOLOGY will test this hypothesis in a multi-scale imaging approach with three synergistic objectives:
Aim 1 will systematically describe the ultrastructure of an Asgard archaeon by developing high-throughput cryo-electron tomography workflows. It will define cell states and features, quantitatively describe cellular architecture, and create a resource for comprehensive “visual proteomics” workflows.
Aim 2 will leverage this atlas in in situ structural analyses. It will reveal the structure and distribution of Asgard ribosomes, test for eukaryote-like uncoupling of transcription and translation, and uncover potential proto-nuclear hallmarks of the cell bodies.
Aim 3 will spatially map mRNA and protein localization using expansion microscopy to test whether lokiarchaeal cell bodies and protrusions are distinct compartments. It will illuminate the function of lokiarchaeal protrusions and reveal whether localized translation and cytoskeletal transport establish compartment identity.
ARCHAEAOLOGY will resolve how spatial organization preceded eukaryotic complexity to reconstruct the cellular organization of the archaeal ancestor of eukaryotes. These insights will provide the experimental foundation to re-evaluate and develop models of eukaryogenesis. Importantly, these unique approaches will also establish a framework for deciphering the cell biology of non-model organisms by integrated multi-scale imaging.

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Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2026-STG

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Host institution

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution
€ 2 046 786,00
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany
Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Links
Total cost
€ 2 046 786,00

Beneficiaries (1)