Wollweber Group

The Wollweber group develops and applies multi-scale imaging methods – such as cryo-electron tomography and expansion microscopy – to decipher the cell biology of non-model organisms and understand the evolution of complex life.

Previous and current research

The origin of eukaryotes and their membrane-bound organelles is one of biology’s biggest mysteries. It can be traced back to an endosymbiotic event involving at least two cells: the bacterial ancestor of mitochondria and an Asgard archaeon. Intriguingly, the genomes of modern Asgard archaea encode close homologues of proteins that were once thought to be unique to eukaryotes. Studying Asgard cell biology remains challenging, however, as they grow very slowly, in mixed cultures with syntrophic partners, and are not genetically tractable. We use multi-scale imaging methods that bridge structural and cell biology to investigate a variety of non-model organisms, including Asgard archaea, to test and develop hypotheses of eukaryogenesis.

Using cryo-electron tomography (cryoET) and super-resolution light microscopy we described the ultrastructure of an enriched Asgard archaeon (Rodrigues-Oliveira*, Wollweber*, Ponce-Toledo* et al., 2023 Nature), revealing a complicated and pleomorphic cell architecture with membranous protrusions and an unusual cell envelope. Our data also uncovered an extended cytoskeleton formed by Lokiactin – one of the most highly conserved eukaryotic signature proteins of Asgard archaea and a close relative of eukaryotic actin. We later discovered novel Asgard tubulins (Wollweber*, Xu* et al., 2025 Cell) that formed eukaryote-like heterodimers and small microtubules in vitro, which we could visualise in situ using expansion microscopy (ExM). By combining cryoET as a discovery tool with complementary imaging modalities, we were thereby able to illuminate the origin of major cytoskeletal systems found in eukaryotes.

Future projects and goals

We will build on our first insights into Asgard archaeal cell biology to understand the complex cell architecture and its implications for eukaryogenesis. By analysing large cryoET datasets of Asgard archaea in a visual proteomics approach, we will obtain insights into the (functional) compartmentalisation of their cytoplasm. Combining these insights with complementary imaging modalities, such as ExM, we will shed light on key aspects of Asgard archaeal cell biology, such as the role of eukaryotic signature proteins in shaping the complex cell structure. Our long-term goal is to study diverse (unculturable) Asgard lineages and their interactions with other organisms directly in environmental samples.

Finally, we will expand our focus to diverse microbial eukaryotes, especially in the context of endosymbiosis and organelle evolution. To do so, we will develop workflows for the vitrification and correlative cryo-focused ion beam (cryo-FIB) milling of large eukaryotic cells. As for Asgard archaea, we will also adapt our methods to access unculturable organisms directly from their native environments.