The Tans Lab

Organoids

How do tissues self-organize?

Organoids are assemblies of cells that recapitulate organ shape and function. Organoids are currently revolutionizing many aspects of cellular biology, as they allow study of disease-relevant processes outside the body. However, technical challenges have long prevented cellular dynamics to be quantified from time-lapse movies. Over the past years, we have developed AI-driven analysis methods to track all cells within organoids as they grow, divide, move, differentiate into difference functional cell types, and ultimately die. This tool shows the truly fascinating ways in which all these systems self-organize into functional tissues. For instance, we have shown that highly dynamics cross-cellular actin structures detect mechanically weak cells to extrude them form the intestinal epithelium, and that cellular identity choices are not governed by a spatial gradient of signaling molecules but rather by a timer mechanism that starts ticking when two key cell types dissociate from each other. This approach can be broadly applied to different organ cell types, organ systems, but also immune cells, which we are also exploring. We do our organoid work together with my colleague Jeroen van Zon, who runs his group also here at the AMOLF institute.

Key Publications

• Epithelial tension controls intestinal cell extrusion (Science 2025)
• Cell tracking with accurate error prediction (Nature Methods 2025)
• Organoid cell fate dynamics in space and time (Science Advances, 2023)
• Mother cells control daughter cell proliferation in intestinal organoids to minimize proliferation fluctuations (eLife, 2022)
• ppGpp is a bacterial cell size regulator (Current Biology, 2022)
• Bacterial coexistence driven by motility and spatial competition (Nature, 2020)
• Stochasticity of metabolism and growth at the single-cell level (Nature, 2014)

Proteins

How can one protein fold another?

Polysomes are RNA messages decorated by ribosomes, as well as the proteins they produce and other cofactors. While known for decades, their functional purpose has long remained unclear. Recent work by us and others now suggest that polysomes enable cooperation between ribosomes. We mainly use single-molecule tools to mechanistically understand this cooperation. We also exploit RNA sequencing methods to characterize it across the proteome in cells, in collaboration with the Bukau-Kramer lab in Heidelberg. For instance, we have shown how two ribosomes are physically linked via the proteins they are synthesizing, and hence jointly produce protein dimers. Strikingly, such nascent chain interactions can suppress misfolding. These and other findings indicate a wealth of dynamics and regulation occurring within polysomes, which we are exploring. These processes may be relevant to all major cellular processes, as well as to mRNA vaccines and AI-generated protein design.

We have pioneered the use of optical tweezers to study these dynamics of individual protein-chaperone complexes, and are currently exploiting a new range of possibilities afforded by simultaneous single-molecule fluorescence.

Key Publications

• Co-translational ribosome pairing enables native assembly of misfolding-prone subunits (Nature Communications 2025)
• Proteome-wide determinants of co-translational chaperone binding in bacteria (Nature Communications 2025)
• Trigger factor accelerates nascent chain compaction and folding (PNAS 2025)
• Protein chain collapse modulation and folding stimulation by GroEL-ES (Science Advances, 2022)
• Processive extrusion of polypeptide loops by a Hsp100 disaggregase (Nature, 2021)
• Alternative modes of client binding enable functional plasticity of Hsp70 (Nature, 2016)
• Small heat shock proteins sequester misfolding proteins in near-native conformation for cellular protection and efficient refolding (Nature Communications, 2016)
• Reshaping of the conformational search of a protein by the chaperone trigger factor (Nature, 2013)
• Direct Observation of Chaperone-Induced Changes in a Protein Folding Pathway (Science, 2007)