Exploring the evolutionary mysteries of the nucleus through revolutionary microscopy techniques
When Gautam Dey peers through his microscope, he isn't just examining cells—he's looking back in time, unraveling mysteries that span two billion years of evolutionary history. As a group leader at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, Dey investigates one of biology's most fundamental questions: how did the cell nucleus, the control center of eukaryotic cells, first evolve? 2
Studying how the cell's control center evolved over two billion years
Examining diverse organisms from fungi to marine protists
Mapping cellular features across the tree of life
"Why does it have such fundamental functions yet have evolved in so many different ways to address those functions?" 2
This Indian-born scientist, who grew up moving between Cyprus, Switzerland, and India before settling into academic life, leads research that sits at the intersection of evolutionary biology, cell biology, and microscopy. His work exemplifies how asking fundamental questions about life's history can lead to unexpected breakthroughs with far-reaching implications. 2
The COVID-19 pandemic forced scientists worldwide to rethink their approaches to research. For Gautam Dey, a Zoom call with collaborator Omaya Dudin during this period sparked a revolutionary research direction. Dudin had successfully adapted a new imaging method to visualize the inner organization of Ichthyosporea, a marine protist closely related to animals and fungi. 1 8
This technique, known as ultrastructure expansion microscopy (U-ExM), overcame a long-standing obstacle: the species' tough cell walls that had previously blocked detailed imaging. 1 The breakthrough was so significant that Dudin immediately recognized its broader potential, telling Dey, "Hey, we should do this with all microbial eukaryotes." 8
Pandemic Zoom call sparks collaboration
Initial U-ExM adaptation for Ichthyosporea
Expansion to hundreds of protist species
PlanExM project and publication in Cell
"This pandemic-era conversation grew into a three-year collaboration that has since produced an unprecedented body of knowledge about hundreds of protist species and laid the groundwork for a 'planetary atlas' of plankton." 1
Expansion microscopy, which marks its 10th anniversary in 2025, operates on a brilliantly simple principle: instead of using complex lenses to magnify tiny structures, it physically enlarges the biological samples themselves. 1 8
"When combined with regular light microscopy methods, expansion microscopy allows scientists to bypass the standard wavelength barriers which limit how small a structure can be resolved using light microscopy," explained University of Geneva scientists Paul Guichard and Virginie Hamel, who refined the original MIT-developed technique. 1
The EMBL-led Traversing European Coastlines (TREC) expedition provided Dey and his collaborators with an ideal opportunity to explore marine microorganisms further. When the team arrived at the Station Biologique in Roscoff, France—home to one of Europe's most comprehensive collections of marine microorganisms—they expected to receive a few dozen samples to test their technique. Instead, they gained access to over 200 species. 1 8
"We spent three days and nights just fixing those samples. This was a treasure trove we could not let go of," said Felix Mikus, who completed his PhD in the Dey Group and is now a postdoc at the University of Geneva. 1 8
This massive sampling effort formed the foundation of what would become PlanExM, a TREC project designed to map the hidden structural diversity of plankton using expansion microscopy. 1 The scale of the project allowed the team to conduct one of the most comprehensive studies ever of the cytoskeleton—the filament network that supports and organizes eukaryotic cells. 8
The research team employed a systematic approach to map cellular structures across diverse plankton species: 1 8
Published in the journal Cell, the study revealed an astonishing diversity of cytoskeletal architectures across the eukaryotic tree of life. 1 6 The team focused specifically on microtubules (hollow filaments that help cells maintain shape, divide, and move) and centrins (proteins involved in organizing microtubules). 1
"We were able to map features of microtubule and centrin organization across many different eukaryotic groups," explained Hiral Shah, EIPOD Postdoctoral Fellow in EMBL's Dey and Schwab groups and co-first author of the study. "The scale of the study, with many species characterized in each group, opens up the possibility to make evolutionary predictions." 1 8
| Eukaryotic Group | Key Microtubule Features Discovered | Evolutionary Significance |
|---|---|---|
| Dinoflagellates | Tubulin and centrin structures associated with cell cortex or flagella | Insights into adaptations of one of the most diverse marine groups |
| Ichthyosporea | Unique mitotic structures | Understanding early evolution of animals and fungi |
| Diatoms | Novel microtubule organization patterns | Revealing adaptations to silica cell walls |
Perhaps most significantly, the research demonstrated how cellular architecture has diversified across evolution. "U-ExM is transforming how we explore protist ultrastructure," said Armando Rubio Ramos, co-first author and Postdoctoral Fellow at the University of Geneva. "It's a bridge between molecular data and the physical organization of life at the microscopic scale." 1 8
| Feature | Traditional Microscopy | Expansion Microscopy |
|---|---|---|
| Resolution | Limited by light wavelength | Bypasses diffraction limits through physical expansion |
| Sample Requirements | Often requires genetic modification | Works with unmodified environmental samples |
| Throughput | Lower due to complex preparation | Enables high-throughput imaging of diverse species |
| Cost | Often requires expensive super-resolution systems | Accessible with conventional microscopes |
Dey's research relies on an innovative combination of classical and cutting-edge approaches. His laboratory employs three parallel experimental strategies: 2
Working with multiple model systems including fungi, deep-branching relatives of animals, and slime moulds
Linking cellular phenotypes to genomes and proteomes across species
Observing cellular evolution in real-time using yeast models
This multi-pronged approach allows the Dey lab to tackle evolutionary questions from multiple angles, combining observations from naturally evolved organisms with experimental evolution in the laboratory.
| Tool/Technique | Function | Application in Dey's Research |
|---|---|---|
| Ultrastructure Expansion Microscopy (U-ExM) | Physically expands biological samples for super-resolution imaging | Visualizing intracellular structures across diverse microbial eukaryotes 1 7 8 |
| Cryo-fixation (High-pressure freezing) | Preserves cellular structures in near-native state | Studying delicate organisms like diatoms with silica cell walls 6 |
| Phylogenetic Analysis | Maps evolutionary relationships between species | Connecting cellular features to evolutionary history 2 |
| Experimental Laboratory Evolution | Observes real-time evolution of model organisms | Testing evolutionary hypotheses under controlled conditions 2 4 |
| Immunofluorescence with Specific Antibodies | Labels specific proteins or structures | Identifying molecular components of cellular structures 7 |
Dey's fundamental research on the evolution of cellular structures has surprising relevance for addressing pressing global challenges. In April 2025, he helped organize an EMBO Workshop titled "Integrating cell and planetary scales to address climate resilience," which brought together scientists from cell biology, climate science, policy, and funding agencies. 3
This workshop highlighted the critical role that fundamental cell biology can play in understanding and addressing climate change. As researchers like Dey uncover how microorganisms adapt their cellular structures to environmental changes, this knowledge could inform strategies for enhancing ecosystem resilience.
"As with all basic research, it is not always obvious what the applications are – or will be, one day in the hypothetical future. We make the broader argument that when you study a fundamental question and try to understand how something works, the applications will naturally follow, often in completely unanticipated ways." 2
His recognition as an EMBO Young Investigator in 2024 further validates the significance of his approach, providing networking, training, and mentorship opportunities along with financial support. 5
With a prestigious $2 million Moore Foundation Grant secured in collaboration with Thomas Richards from Oxford University and Omaya Dudin, Dey's research program is poised for even greater discoveries. 1 8 "The next step," according to Dudin, "is to selectively look deeper into certain species within this broad collection to answer specific questions, such as understanding how mitosis and multicellularity evolved and the phenotypic diversity that underlie major evolutionary transitions." 1
"Our adventures with expansion microscopy are only beginning. This is perhaps the first high-resolution microscopy technique that has the potential to match the scale and ambition of large biodiversity genomics projects, enabling us in the near future to associate new multiomics data with cellular physiology at scale across the tree of life." 1
His advice for future scientists reflects both his idealism and practical experience: "We live in uncertain times, when fundamental research seems like a luxury we can ill-afford in the face of pandemics, climate change, and war. Of course, what we really should be doing is pouring even more money into basic science. It is from an open-ended search for knowledge that our most transformative discoveries have emerged." 2
As Dey and his team continue to expand both our microscopic view of cellular structures and our understanding of life's evolutionary history, they demonstrate how curiosity-driven science can reveal profound truths about the natural world while building foundations for future innovations. In the invisible world of microscopic organisms, they're discovering clues to life's biggest mysteries—one expanded cell at a time.