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Agnes Backhausz, Christian Kuehn, Sjoerd van der Niet, Giulio Zucal
Spectral theory of dense hypergraph limits
DISCRETE MATHEMATICS, 350(1) Art. No. 115362 (2027)
Open Access Source   

In this work, we develop a spectral theory for hypergraph limits. We prove the convergence of the spectra of adjacency and Laplacian matrices for hypergraph sequences converging in the 1-cut metric. On the other hand, we give examples of matrix operators associated with hypergraphs whose spectra are not continuous with respect to the 1-cut metric. Furthermore, we show that these operators are continuous with respect to other cut norms
@article{Backhausz9288,
author={Agnes Backhausz, Christian Kuehn, Sjoerd van der Niet, Giulio Zucal},
title={Spectral theory of dense hypergraph limits},
journal ={DISCRETE MATHEMATICS},
volume={350},
issue ={1},
pages={null--null},
year=2027
}

Marion K Raich, Fridtjof Brauns, Tamara Müller, Maximilian Reichert, Andreas R Bausch
Multicellular rosette formation guides epithelial tissue assembly in pancreatic ductal adenocarcinoma cell organoids.
Proc Natl Acad Sci U.S.A., 123(37) Art. No. e2512284123 (2026)
PubMed Source   

Mesenchymal-to-epithelial transitions are essential for epithelial tissue formation and thus the development of functional organs. Here, we demonstrate that the transition from a disordered mesenchymal state to a columnar epithelial structure in branched pancreatic ductal adenocarcinoma organoids is associated with rosette formation. We show that fluctuations in acto-myosin contractions on the emerging apical side of branches with high cell density create a tug-of-war mechanism, leading to regular spacing of rosettes. The distance between adjacent rosettes depends on the branch diameter, which we validate with a minimal theoretical model based on apical constriction. The resulting lumen formation occurs through the apoptosis of an inner cell mass, leaving an epithelial layer lining the cavity. In summary, our findings show that rosette architecture is set by geometrical confinement of the cell nuclei in combination with acto-myosin driven contractions. This underscores the critical role of mechanical processes in self-organized assembly of epithelial tissue.
@article{Raich9307,
author={Marion K Raich, Fridtjof Brauns, Tamara Müller, Maximilian Reichert, Andreas R Bausch},
title={Multicellular rosette formation guides epithelial tissue assembly in pancreatic ductal adenocarcinoma cell organoids.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={123},
issue ={37},
pages={null--null},
year=2026
}

Mitsuhiro Matsuda, Henrik M Hammarén, Jorge Lázaro, Mikhail M Savitski#, Miki Ebisuya#
Systematic differences in protein stability underlie species-specific developmental tempo.
Dev Cell, 61(9) 1855-1866 (2026)
Open Access PubMed Source   

Human embryonic development proceeds more slowly than in mice. The segmentation clock offers a tractable model for studying species-specific developmental tempo, as its oscillation period in human induced presomitic mesoderm (iPSM) cells is approximately twice that of mouse. While the core clock gene HES7 exhibits slower protein degradation in human cells, it remains unclear whether such cross-species differences in protein stability reflect a general principle. Here, we perform a dynamic stable isotope labeling of amino acids in cell culture (SILAC)-based proteomic analysis of ∼5,000 proteins in human and mouse iPSM, and we uncover a broad trend of slower protein degradation in human cells, regardless of subcellular localization or degradation pathways. Moreover, inhibition of glycolysis in mouse iPSM partially phenocopies the human protein stability profile, and modulation of protein stability alters the tempo of both the segmentation clock and cellular differentiation. Our findings establish protein stability, with systematic differences across species, as a key mediator linking metabolism to developmental tempo.
@article{Matsuda9291,
author={Mitsuhiro Matsuda, Henrik M Hammarén, Jorge Lázaro, Mikhail M Savitski, Miki Ebisuya},
title={Systematic differences in protein stability underlie species-specific developmental tempo.},
journal ={Developmental cell},
volume={61},
issue ={9},
pages={1855--1866},
year=2026
}

Anna Dowbaj#, Meritxell Huch#
Liver organoids: modelling complexity in homeostasis and disease.
FEBS Lett, Art. No. doi: 10.1002/1873-3468.70432 (2026)
Open Access PubMed Source   

Liver is a complex organ, capable of incredible regenerative capacity in the mammalian body. In addition to well-known hepatocytes, liver is composed of a complex cell microenvironment, with each cell type contributing to homeostasis, regeneration and disease. Modelling of the liver in vitro has been hampered by 2D cell lines being too simple and whole animal models too complex to underpin the mechanisms of liver biology. Liver organoids are emerging as a great tool to study liver (patho)physiology. Increasing in complexity, organoids have successfully been used to understand the cellular interplay in genetic and metabolic liver diseases, as well as liver cancer. This review will discuss the advancement in modelling cell complexity, maturation and liver architecture in a Petri dish. It will also provide a state-of-the-art perspective of what is still lacking and how the models can be further improved. Finally, we will conclude with our personal vision of where the field is going.
@article{Dowbaj9303,
author={Anna Dowbaj, Meritxell Huch},
title={Liver organoids: modelling complexity in homeostasis and disease.},
journal ={FEBS letters},
volume={},
pages={1--1},
year=2026
}

Mihaly Badonyi#, Agnes Toth-Petroczy#
A simple probabilistic AlphaFold interaction score.
Protein Sci, 35(9) Art. No. e70760 (2026)
Open Access PubMed Source   

AlphaFold has enabled large-scale prediction of protein-protein and protein-nucleic acid complexes, but ranking and assessing the quality of predicted models remain challenging. Existing confidence scores are often highly parametrized and provide limited interpretability. We introduce a simple geometric framework that converts AlphaFold-predicted aligned error (PAE) into conditional contact probability. We show that these probabilities are well calibrated to the fraction of native contacts observed across experimentally determined structures. Motivated by this, we define the Pinc score (Probability of interface native contacts) as the mean contact probability between interacting chains. Because the probabilistic interpretation extends to individual residues, Pinc captures local structural constraint beyond interfacial burial, enabling residue-level prioritization of hotspot positions for mutational studies. Depending solely on a single empirically fixed contact radius, Pinc offers an interpretable path from PAE to interface confidence, matching or exceeding the classification performance of more complex methods across five independent benchmark sets. We provide a portable, dependency-free C program and a Google Colab notebook for calculating Pinc scores for AlphaFold models at https://git.mpi-cbg.de/tothpetroczylab/Pinc.
@article{Badonyi9294,
author={Mihaly Badonyi, Agnes Toth-Petroczy},
title={A simple probabilistic AlphaFold interaction score.},
journal ={Protein science : a publication of the Protein Society},
volume={35},
issue ={9},
pages={null--null},
year=2026
}

Nada Mohamad*, Siu-Shing Wong*, Anupa Majumdar*, Alan Wainman, Ingelise Holland-Kaye, Lars Hubatsch, Zsofia Novak, Andrei I. Pozniakovsky, Martine Ruer-Gruss, Andreas F M Haensele, Anna Caballe, Steven Johnson, Susan M Lea#, Anthony Hyman#, Jordan W Raff#
Polo/PLK1 phosphorylation relieves Centrosomin/Cnn autoinhibition to promote centrosome scaffold assembly.
EMBO J, 45(17) 6320-6356 (2026)
Open Access PubMed Source   

Mitotic centrosome maturation requires Polo/PLK1-dependent expansion of the pericentriolar material (PCM). In Drosophila, Centrosomin (Cnn) assembles a scaffold around mitotic centrioles through interactions between its PReM and CM2 domains. Here, we show that PReM adopts an autoinhibited helical hairpin conformation that prevents CM2 binding. Polo/PLK1 phosphorylation relieves this autoinhibition, enabling scaffold assembly, whereas phospho-blocking mutations disrupt PReM-CM2 binding in vitro and Cnn scaffold assembly in vivo. Potential functionally analogous domains have been identified in the human and C. elegans Cnn homologues CDK5RAP2 and SPD-5. We find that the human protein appears to share a structurally similar mechanism for scaffold assembly, but the worm protein does not. Consistent with this, deletion of these domains alters the dynamics of Cnn condensates in vitro, but has little effect on SPD-5 condensate dynamics. We conclude that Polo/PLK1 promotes mitotic centrosome assembly, at least in part, by relieving autoinhibitory intramolecular interactions.
@article{Mohamad9280,
author={Nada Mohamad, Siu-Shing Wong, Anupa Majumdar, Alan Wainman, Ingelise Holland-Kaye, Lars Hubatsch, Zsofia Novak, Andrei I. Pozniakovsky, Martine Ruer-Gruss, Andreas F M Haensele, Anna Caballe, Steven Johnson, Susan M Lea, Anthony Hyman, Jordan W Raff},
title={Polo/PLK1 phosphorylation relieves Centrosomin/Cnn autoinhibition to promote centrosome scaffold assembly.},
journal ={The EMBO journal},
volume={45},
issue ={17},
pages={6320--6356},
year=2026
}

Eugene Christo V R*, Christoph Robert Meinecke*, Bert Nitzsche, Roman Lyttleton, Cordula Reuther, Danny Reuter, Heiner Linke, Till Korten#, Stefan Diez#
Practically Error-Free Junctions Enable Solving Large Instances of Exact Cover Problems Using Network-Based Biocomputation.
Small, Art. No. doi: 10.1002/smll.75307 (2026)
Open Access PubMed Source   

Network-based biocomputing (NBC) presents an energy-efficient, parallel computing approach for solving nondeterministic polynomial time (NP) complete problems by leveraging motor-driven cytoskeletal filaments that explore all possible solutions through nanofabricated networks in a massively parallel fashion. However, guiding errors at pass junctions, where filaments deviate from their intended path, currently limit the scalability of NBC systems. In this study, we addressed this critical challenge by fabricating sub-200 nm channel geometries using modified electron-beam-lithography and reactive-ion-etching protocols to physically constrain the trajectories of kinesin-driven microtubules and enhance path fidelity. Investigating junction designs with varying channel widths, we demonstrate that reducing channel width significantly lowers junction error rates. Practically error-free junction performance was achieved by scaling down the entire network geometry by a factor of two. These optimized junctions were incorporated into NBC networks that successfully solved 24- and 25-set instances of the Exact Cover problem, representing solution spaces of approximately 16 and 33 million, respectively. This work establishes a new benchmark in NBC performance and represents a computational scale far beyond what has been achieved in prior demonstrations.
@article{R9298,
author={Eugene Christo V R, Christoph Robert Meinecke, Bert Nitzsche, Roman Lyttleton, Cordula Reuther, Danny Reuter, Heiner Linke, Till Korten, Stefan Diez},
title={Practically Error-Free Junctions Enable Solving Large Instances of Exact Cover Problems Using Network-Based Biocomputation.},
journal ={Small (Weinheim an der Bergstrasse, Germany)},
volume={},
pages={1--1},
year=2026
}

Branislava Rankovic*, Zachary M Geisterfer*, Akshita Chhabra, Vladimir M Jovanovic, Ian Seim, Christian Hoffmann, Antonela Condric, Gerard Aguilar Pérez, Rinse de Boer, Lars T Hofstede, Jingao Sun, Kiara Freitag, Katja Nowick, Marina Jendrach, Frank L Heppner, Vladimir Despic, Michaela Müller-McNicoll, Stephan J Sigrist, Geert van den Bogaart, Sofiia Reshetniak, Amy Gladfelter#, Dragomir Milovanovic#
RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System.
Adv Sci (Weinh), Art. No. doi: 10.1002/advs.77115 (2026)
Open Access PubMed Source   

Condensates at synapses organize synaptic vesicle (SV) clusters and are essential for efficient neurotransmitter release. While it is established that RNA granules traffic along axons, the function of RNA at the presynapse remains unclear. Here, we uncover a direct structural role of coding RNAs in organizing presynaptic condensates by focusing on SV clusters, condensates between synapsin-1 and lipid vesicles. Using in vitro reconstitution systems, we show that RNA drives synapsin-1 coacervation, with structured RNAs being more effective at promoting phase transitions. The importance of RNA was confirmed in living synapses, where acute disruption of native RNA induces a dispersion of SVs and synapsin. Conversely, ectopically expressed SV-like condensates contained the translational machinery. The microscopy-based in vitro translation assay demonstrates increased translation efficiency within synapsin-1/RNA condensates. Together, our work indicates a novel structural role of RNAs in modulating SV condensates.
@article{Rankovic9301,
author={Branislava Rankovic, Zachary M Geisterfer, Akshita Chhabra, Vladimir M Jovanovic, Ian Seim, Christian Hoffmann, Antonela Condric, Gerard Aguilar Pérez, Rinse de Boer, Lars T Hofstede, Jingao Sun, Kiara Freitag, Katja Nowick, Marina Jendrach, Frank L Heppner, Vladimir Despic, Michaela Müller-McNicoll, Stephan J Sigrist, Geert van den Bogaart, Sofiia Reshetniak, Amy Gladfelter, Dragomir Milovanovic},
title={RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System.},
journal ={Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume={},
pages={1--1},
year=2026
}

Elizabeth Eck, Bruno Moretti, Brandon H Schlomann, Jordão Bragantini, Merlin Lange, Xiang Zhao, Shruthi VijayKumar, Guillaume Valentin, Cristina Loureiro, Pablo Perez Franco, Chloé Jollivet, Virginie Braman, Baldemar Motomochi, Loic Royer, Andrew C. Oates#, Hernan G Garcia#
Single-cell transcriptional dynamics in a living vertebrate.
Cell Syst, Art. No. 10.1016/j.cels.2026.101708 (2026)
PubMed Source   

The ability to follow transcription in individual cells with live imaging has revealed key dynamical mechanisms of gene regulation. However, such measurements are lacking in the context of vertebrate embryos. We addressed this deficit by applying MS2-MCP mRNA labeling to the quantification of transcription in zebrafish, a model vertebrate. We developed a platform of transgenic organisms, light-sheet fluorescence microscopy, and optimized image analysis that enables visualization and quantification of MS2 reporters. With these tools, we obtained single-cell, real-time measurements of the transcriptional dynamics of the segmentation clock. Our measurements reveal that smooth clock protein oscillations arise from discrete transcriptional bursts that are organized in space and time. Together, these results highlight how measuring single-cell transcriptional activity in the context of vertebrate organisms can reveal unexpected features of gene regulation and how this data can fuel the dialogue between theory and experiment.
@article{Eck9293,
author={Elizabeth Eck, Bruno Moretti, Brandon H Schlomann, Jordão Bragantini, Merlin Lange, Xiang Zhao, Shruthi VijayKumar, Guillaume Valentin, Cristina Loureiro, Pablo Perez Franco, Chloé Jollivet, Virginie Braman, Baldemar Motomochi, Loic Royer, Andrew C. Oates, Hernan G Garcia},
title={Single-cell transcriptional dynamics in a living vertebrate.},
journal ={Cell systems},
volume={},
pages={101708--101708},
year=2026
}

Archishman Ghosh, Advait Thatte, Surased Suraritdechachai, Roman Rattunde, Christoph A. Weber#, T Y Dora Tang#
Transcription-driven phase separation of synthetic condensates enables self-organizing compartments and protective microenvironments
CELL REPORTS PHYSICAL SCIENCE, 7(8) Art. No. 103481 (2026)
Open Access Source   

We show that coupling enzymatic activity to condensation under limited resource conditions drives emergent self-regulation via droplet formation and dissolution. Our kinetic models show that in situ phase separation of in-vitro-transcribed mRNA with an intrinsically disordered protein (mutant G3BP1) modulates transcription and degradation kinetics. When resources for mRNA production are limited, condensates spontaneously dissolve, driven by the feedback from compartmentalization on reaction rate constants-with slower degradation within condensates than in the mRNA-protein-poor phase. Consequently, the lifetime of mRNA is prolonged upon condensation compared to the case without condensates. Extending the model to sustained and oscillatory resource supply reveals that condensates elevate mean mRNA levels and buffer deviations from the mean compared to the non-condensate scenario. These findings provide a general mechanism of cross-regulation and feedback between phase separation and enzymatic reactions, highlighting condensates as active regulators of biochemical flux rather than as passive organizers.
@article{Ghosh9292,
author={Archishman Ghosh, Advait Thatte, Surased Suraritdechachai, Roman Rattunde, Christoph A. Weber, T Y Dora Tang},
title={Transcription-driven phase separation of synthetic condensates enables self-organizing compartments and protective microenvironments},
journal ={CELL REPORTS PHYSICAL SCIENCE},
volume={7},
issue ={8},
pages={null--null},
year=2026
}
* joint first authors, # joint corresponding authors