Prof. Sander Tans, AMOLF Amsterdam
Invited by Prof. Steffen Rulands and Prof. Erwin Frey
The colloquium will be streamed online.
In this talk, I will cover recent organoid and single-molecule work from our group.
In the first1-3, we studied how the proper number of cells is maintained in rapidly renewing organs like the intestine. It was previously thought that cellular proliferation leads to crowding and compression, which in turn triggers cell extrusion from the epithelium. To address this question, we developed tools ranging from long term 3D imaging organoids, AI-driven cell tracking, opto-genetic control of cellular forces, and tension measurements in intestinal explants. Our data rather shows that cell extrusion is triggered in mechanically weak cells, with cells continuously engaging in a dynamic tug-of-war to assess their mechanical state.
In the second4,5, we wonder how protein complexes can be assembled despite their often intertwined structures. Here, we used methods including optical tweezers to manipulate individual ribosomes, single-molecule fluorescence to assess protein-protein interactions, and selective ribosome profiling to study assembly throughout the proteome. We found that protein dimers are ubiquitously assembled while they are still being translated by ribosomes. This mechanism suppresses major misfolding events, and hence expands the space of possible proteins. These findings indicate that ribosomes cooperate which has many possible implications for their regulation within the cell.
1 Krueger, D., Spoelstra, W. K., Mastebroek, D. J., Kok, R. N. U., Wu, S., Nikolaev, M., Bannier-Helaouet, M., Gjorevski, N., Lutolf, M., van Es, J., van Zon, J., Tans, S. J. & Clevers, H. Epithelial tension controls intestinal cell extrusion. Science 389, (2025).
2 Betjes, M. A., Kok, R. N. U., Tans, S. J. & van Zon, J. S. Cell tracking with accurate error prediction. Nat Methods, (2025).
3 Zheng, X., Betjes, M. A., Ender, P., Goos, Y. J., Huelsz-Prince, G., Clevers, H., van Zon, J. S. & Tans, S. J. Organoid cell fate dynamics in space and time. Sci Adv 9, (2023).
4 Bertolini, M., Fenzl, K., Kats, I., Wruck, F., Tippmann, F., Schmitt, J., Auburger, J. J., Tans, S., Bukau, B. & Kramer, G. Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly. Science 371, (2021).
5 Wruck, F., Schmitt, J., Till, K., Fenzl, K., Bertolini, M., Tippmann, F., Katranidis, A., Bukau, B., Kramer, G. & Tans, S. J. Co-translational ribosome pairing enables native assembly of misfolding-prone subunits. Nature communications 16, (2025).