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Daxiao Sun#, Xueping Zhao, Tina Wiegand, Cécilie Martin-Lemaitre, Tom Borianne, Lennart Kleinschmidt, Stephan W. Grill, Anthony Hyman, Christoph A. Weber#, Alf Honigmann#
Assembly of tight junction belts by ZO1 surface condensation and local actin polymerization.
Dev Cell, Art. No. doi: 10.1016/j.devcel.2024.12.012 (2025)
Open Access PubMed Source   

Tight junctions play an essential role in sealing tissues, by forming belts of adhesion strands around cellular perimeters. Recent work has shown that the condensation of ZO1 scaffold proteins is required for tight junction assembly. However, the mechanisms by which junctional condensates initiate at cell-cell contacts and elongate around cell perimeters remain unknown. Combining biochemical reconstitutions and live-cell imaging of MDCKII tissue, we found that tight junction belt formation is driven by adhesion receptor-mediated ZO1 surface condensation coupled to local actin polymerization. Adhesion receptor oligomerization provides the signal for surface binding and local condensation of ZO1 at the cell membrane. Condensation produces a molecular scaffold that selectively enriches junctional proteins. Finally, ZO1 condensates directly facilitate local actin polymerization and filament bundling, driving the elongation into a continuous tight junction belt. More broadly, our work identifies how cells couple surface condensation with cytoskeleton organization to assemble and structure adhesion complexes.
@article{Sun8882,
author={Daxiao Sun, Xueping Zhao, Tina Wiegand, Cécilie Martin-Lemaitre, Tom Borianne, Lennart Kleinschmidt, Stephan W. Grill, Anthony Hyman, Christoph A. Weber, Alf Honigmann},
title={Assembly of tight junction belts by ZO1 surface condensation and local actin polymerization.},
journal ={Developmental cell},
volume={},
pages={1--1},
year=2025
}

Anne Grapin-Botton#, Jonathan Y-H Loh#
Editorial overview: Regaining architecture and cell cross-talk upon regeneration.
Curr Opin Genet Dev, 91 Art. No. 102302 (2025)
PubMed Source  

@article{Grapin-Botton8881,
author={Anne Grapin-Botton, Jonathan Y-H Loh},
title={Editorial overview: Regaining architecture and cell cross-talk upon regeneration.},
journal ={Current opinion in genetics & development},
volume={91},
pages={null--null},
year=2025
}

Helen M Byrne#, Heather A Harrington#, Alexey Ovchinnikov#, Gleb Pogudin#, Hamid Rahkooy#, Pedro Soto#
Algebraic identifiability of partial differential equation models
NONLINEARITY, 38(2) Art. No. 025022 (2025)
Open Access Source   

Differential equation models are crucial to scientific processes across many disciplines, and the values of model parameters are important for analyzing the behaviour of solutions. Identifying these values is known as a parameter estimation, a type of inverse problem, which has applications in areas that include industry, finance and biomedicine. A parameter is called globally identifiable if its value can be uniquely determined from the input and output functions. Checking the global identifiability of model parameters is a useful tool when exploring the well-posedness of a given model. This problem has been intensively studied for ordinary differential equation models, where theory, several efficient algorithms and software packages have been developed. A comprehensive theory for PDEs has hitherto not been developed due to the complexity of initial and boundary conditions. Here, we provide theory and algorithms, based on differential algebra, for testing identifiability of polynomial PDE models. We showcase this approach on PDE models arising in the sciences.
@article{Byrne8898,
author={Helen M Byrne, Heather A Harrington, Alexey Ovchinnikov, Gleb Pogudin, Hamid Rahkooy, Pedro Soto},
title={Algebraic identifiability of partial differential equation models},
journal ={NONLINEARITY},
volume={38},
issue ={2},
pages={null--null},
year=2025
}

Christoph Zechner#, Frank Jülicher#
Concentration buffering and noise reduction in non-equilibrium phase-separating systems.
Cell Syst, Art. No. doi: 10.1016/j.cels.2025.101168 (2025)
Open Access PubMed Source   

Biomolecular condensates have been proposed to buffer intracellular concentrations and reduce noise. However, concentrations need not be buffered in multicomponent systems, leading to a non-constant saturation concentration (csat) when individual components are varied. Simplified equilibrium considerations suggest that noise reduction might be closely related to concentration buffering and that a fixed saturation concentration is required for noise reduction to be effective. Here, we present a theoretical analysis to demonstrate that these suggestions do not apply to mesoscopic fluctuating systems. We show that concentration buffering and noise reduction are distinct concepts, which cannot be used interchangeably. We further demonstrate that concentration buffering and a constant csat are neither necessary nor sufficient for noise reduction to be effective. Clarity about these concepts is important for studying the role of condensates in controlling cellular noise and for the interpretation of concentration relationships in cells. A record of this paper's transparent peer review process is included in the supplemental information.
@article{Zechner8896,
author={Christoph Zechner, Frank Jülicher},
title={Concentration buffering and noise reduction in non-equilibrium phase-separating systems.},
journal ={Cell systems},
volume={},
pages={null--null},
year=2025
}

Leon Hilgers#, Shenglin Liu, Axel Jensen, Thomas Brown, Trevor Cousins, Regev Schweiger, Katerina Guschanski, Michael Hiller#
Avoidable false PSMC population size peaks occur across numerous studies.
Curr Biol, Art. No. doi: 10.1016/j.cub.2024.09.028 (2025)
Open Access PubMed Source   

Inferring historical population sizes is key to identifying drivers of ecological and evolutionary change and crucial to predicting the future of species on our rapidly changing planet. The pairwise sequentially Markovian coalescent (PSMC) method provided a revolutionary framework to reconstruct species' demographic histories over millions of years based on the genome sequence of a single individual. Here, we detected and solved a common artifact in PSMC and related methods: recent population peaks followed by population collapses. Combining real and simulated genomes, we show that these peaks do not represent true population dynamics. Instead, ill-set default parameters cause false peaks in our own and published data, which can be avoided by adjusting parameter settings. Furthermore, we show that certain changes in population structure can cause similar patterns. Newer methods, like Beta-PSMC, perform better but do not always avoid this artifact. Our results suggest testing multiple parameters that split the first time window before interpreting recent population peaks followed by collapses and call for the development of robust methods.
@article{Hilgers8897,
author={Leon Hilgers, Shenglin Liu, Axel Jensen, Thomas Brown, Trevor Cousins, Regev Schweiger, Katerina Guschanski, Michael Hiller},
title={Avoidable false PSMC population size peaks occur across numerous studies.},
journal ={Current biology : CB},
volume={},
pages={1--1},
year=2025
}

Yitong Xu, Anna Chao, Melissa Rinaldin, Alison Kickuth, Jan Brugués, Stefano Di Talia
The cell cycle oscillator and spindle length set the speed of chromosome separation in Drosophila embryos.
Curr Biol, 35(3) 655-664 (2025)
PubMed Source   

Anaphase is tightly controlled spatiotemporally to ensure proper separation of chromosomes.1,2,3 The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm.4,5,6,7 Yet, the relationship between spindle size and chromosome movement remains poorly understood. Here, we address this relationship during the cleavage divisions of the Drosophila blastoderm. We show that the speed of chromosome separation gradually decreases during the four nuclear divisions of the blastoderm. This reduction in speed is accompanied by a similar reduction in spindle length, ensuring that these two quantities are tightly linked. Using a combination of genetic and quantitative imaging approaches, we find that two processes contribute to controlling the speed at which chromosomes move in anaphase: the activity of molecular motors important for microtubule depolymerization and sliding and the cell cycle oscillator. Specifically, we found that the levels of multiple kinesin-like proteins important for microtubule depolymerization, as well as kinesin-5, contribute to setting the speed of chromosome separation. This observation is further supported by the scaling of poleward flux rate with the length of the spindle. Perturbations of the cell cycle oscillator using heterozygous mutants of mitotic kinases and phosphatases revealed that the duration of anaphase increases during the blastoderm cycles and is the major regulator of chromosome velocity. Thus, our work suggests a link between the biochemical rate of mitotic exit and the forces exerted by the spindle. Collectively, we propose that the cell cycle oscillator and spindle length set the speed of chromosome separation in anaphase.
@article{Xu8885,
author={Yitong Xu, Anna Chao, Melissa Rinaldin, Alison Kickuth, Jan Brugués, Stefano Di Talia},
title={The cell cycle oscillator and spindle length set the speed of chromosome separation in Drosophila embryos.},
journal ={Current biology : CB},
volume={35},
issue ={3},
pages={655--664},
year=2025
}

Max Dongsheng Yin*, Olivier N Lemaire*, José Guadalupe Rosas Jiménez, Mélissa Belhamri, Anna Shevchenko, Gerhard Hummer#, Tristan Wagner#, Bonnie J Murphy#
Conformational dynamics of a multienzyme complex in anaerobic carbon fixation.
Science, 387(6733) 498-504 (2025)
PubMed Source   

In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO2) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen Clostridium autoethanogenum, characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO2 reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates. Altogether, the structures allow us to draw a detailed reaction mechanism of this enzyme, which is crucial for CO2 fixation in anaerobic organisms.
@article{Yin8891,
author={Max Dongsheng Yin, Olivier N Lemaire, José Guadalupe Rosas Jiménez, Mélissa Belhamri, Anna Shevchenko, Gerhard Hummer, Tristan Wagner, Bonnie J Murphy},
title={Conformational dynamics of a multienzyme complex in anaerobic carbon fixation.},
journal ={Science (New York, N.Y.)},
volume={387},
issue ={6733},
pages={498--504},
year=2025
}

Srustidhar Das, S Martina Parigi, Xinxin Luo, Jennifer Fransson, Bianca C Kern, Ali Okhovat, Oscar E Diaz, Chiara Sorini, Paulo Czarnewski, Anna T Webb, Rodrigo A Morales, Sacha Lebon, Gustavo Monasterio, Francisca Castillo, Kumar P Tripathi, Ning He, Penelope Pelczar, Nicola Schaltenberg, Marjorie De la Fuente, Francisco López-Köstner, Susanne Nylén, Hjalte List Larsen, Raoul Kuiper, Per Antonson, Marcela A Hermoso, Samuel Huber, Moshe Biton, Sandra Scharaw, Jan-Åke Gustafsson, Pekka Katajisto, Eduardo J Villablanca
Liver X receptor unlinks intestinal regeneration and tumorigenesis.
Nature, 637(8048) 1198-1206 (2025)
Open Access PubMed Source Full Text   

Uncontrolled regeneration leads to neoplastic transformation1-3. The intestinal epithelium requires precise regulation during continuous homeostatic and damage-induced tissue renewal to prevent neoplastic transformation, suggesting that pathways unlinking tumour growth from regenerative processes must exist. Here, by mining RNA-sequencing datasets from two intestinal damage models4,5 and using pharmacological, transcriptomics and genetic tools, we identified liver X receptor (LXR) pathway activation as a tissue adaptation to damage that reciprocally regulates intestinal regeneration and tumorigenesis. Using single-cell RNA sequencing, intestinal organoids, and gain- and loss-of-function experiments, we demonstrate that LXR activation in intestinal epithelial cells induces amphiregulin (Areg), enhancing regenerative responses. This response is coordinated by the LXR-ligand-producing enzyme CYP27A1, which was upregulated in damaged intestinal crypt niches. Deletion of Cyp27a1 impaired intestinal regeneration, which was rescued by exogenous LXR agonists. Notably, in tumour models, Cyp27a1 deficiency led to increased tumour growth, whereas LXR activation elicited anti-tumour responses dependent on adaptive immunity. Consistently, human colorectal cancer specimens exhibited reduced levels of CYP27A1, LXR target genes, and B and CD8 T cell gene signatures. We therefore identify an epithelial adaptation mechanism to damage, whereby LXR functions as a rheostat, promoting tissue repair while limiting tumorigenesis.
@article{Das8847,
author={Srustidhar Das, S Martina Parigi, Xinxin Luo, Jennifer Fransson, Bianca C Kern, Ali Okhovat, Oscar E Diaz, Chiara Sorini, Paulo Czarnewski, Anna T Webb, Rodrigo A Morales, Sacha Lebon, Gustavo Monasterio, Francisca Castillo, Kumar P Tripathi, Ning He, Penelope Pelczar, Nicola Schaltenberg, Marjorie De la Fuente, Francisco López-Köstner, Susanne Nylén, Hjalte List Larsen, Raoul Kuiper, Per Antonson, Marcela A Hermoso, Samuel Huber, Moshe Biton, Sandra Scharaw, Jan-Åke Gustafsson, Pekka Katajisto, Eduardo J Villablanca},
title={Liver X receptor unlinks intestinal regeneration and tumorigenesis.},
journal ={Nature},
volume={637},
issue ={8048},
pages={1198--1206},
year=2025
}

Ariadna E Morales*, Yue Dong*, Thomas Brown, Kaushal Baid, Dimitrios-Georgios Kontopoulos, Victoria Gonzalez, Zixia Huang, Alexis-Walid Ahmed, Arkadeb Bhuinya, Leon Hilgers, Sylke Winkler, Graham M Hughes, Xiaomeng Li, Ping Lu, Yixin Yang, Bogdan Kirilenko, Paolo Devanna, Tanya M Lama, Yomiran Nissan, Martin Pippel, Liliana M Dávalos, Sonja Vernes, Sébastien J Puechmaille, Stephen J Rossiter, Yossi Yovel, Joseph B Prescott, Andreas Kurth, David A Ray, Burton K Lim, Eugene W Myers, Emma Teeling, Arinjay Banerjee, Aaron T Irving#, Michael Hiller#
Bat genomes illuminate adaptations to viral tolerance and disease resistance.
Nature, Art. No. doi: 10.1038/s41586-024-08471-0 (2025)
Open Access PubMed Source   

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order1. Infections in bats are largely asymptomatic2,3, indicating limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, the Bat1K project generated reference-quality genomes of ten bat species, including potential viral reservoirs. Here we describe a systematic analysis covering 115 mammalian genomes that revealed that signatures of selection in immune genes are more prevalent in bats than in other mammalian orders. We found an excess of immune gene adaptations in the ancestral chiropteran branch and in many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15, which is an antiviral gene contributing to hyperinflammation during COVID-19 (refs. 4,5), exhibits key residue changes in rhinolophid and hipposiderid bats. Cellular infection experiments show species-specific antiviral differences and an essential role of protein conjugation in antiviral function of bat ISG15, separate from its role in secretion and inflammation in humans. Furthermore, in contrast to humans, ISG15 in most rhinolophid and hipposiderid bats has strong anti-SARS-CoV-2 activity. Our work reveals molecular mechanisms that contribute to viral tolerance and disease resistance in bats.
@article{Morales8892,
author={Ariadna E Morales, Yue Dong, Thomas Brown, Kaushal Baid, Dimitrios-Georgios Kontopoulos, Victoria Gonzalez, Zixia Huang, Alexis-Walid Ahmed, Arkadeb Bhuinya, Leon Hilgers, Sylke Winkler, Graham M Hughes, Xiaomeng Li, Ping Lu, Yixin Yang, Bogdan Kirilenko, Paolo Devanna, Tanya M Lama, Yomiran Nissan, Martin Pippel, Liliana M Dávalos, Sonja Vernes, Sébastien J Puechmaille, Stephen J Rossiter, Yossi Yovel, Joseph B Prescott, Andreas Kurth, David A Ray, Burton K Lim, Eugene W Myers, Emma Teeling, Arinjay Banerjee, Aaron T Irving, Michael Hiller},
title={Bat genomes illuminate adaptations to viral tolerance and disease resistance.},
journal ={Nature},
volume={},
pages={1--1},
year=2025
}

Aditya Chhatre, Ludek Stepanek, Adrian Pascal Nievergelt, Gonzalo Alvarez Viar, Stefan Diez#, Gaia Pigino#
Tubulin tyrosination/detyrosination regulate the affinity and sorting of intraflagellar transport trains on axonemal microtubule doublets.
Nat Commun, 16(1) Art. No. 1055 (2025)
Open Access PubMed Source   

Cilia assembly and function rely on the bidirectional transport of components between the cell body and ciliary tip via Intraflagellar Transport (IFT) trains. Anterograde and retrograde IFT trains travel along the B- and A-tubules of microtubule doublets, respectively, ensuring smooth traffic flow. However, the mechanism underlying this segregation remains unclear. Here, we test whether tubulin detyrosination (enriched on B-tubules) and tyrosination (enriched on A-tubules) have a role in IFT logistics. We report that knockout of tubulin detyrosinase VashL in Chlamydomonas reinhardtii causes frequent IFT train stoppages and impaired ciliary growth. By reconstituting IFT train motility on de-membranated axonemes and synthetic microtubules, we show that anterograde and retrograde trains preferentially associate with detyrosinated and tyrosinated microtubules, respectively. We propose that tubulin tyrosination/detyrosination is crucial for spatial segregation and collision-free IFT train motion, highlighting the significance of the tubulin code in ciliary transport.
@article{Chhatre8888,
author={Aditya Chhatre, Ludek Stepanek, Adrian Pascal Nievergelt, Gonzalo Alvarez Viar, Stefan Diez, Gaia Pigino},
title={Tubulin tyrosination/detyrosination regulate the affinity and sorting of intraflagellar transport trains on axonemal microtubule doublets.},
journal ={Nature communications},
volume={16},
issue ={1},
pages={null--null},
year=2025
}


* joint first authors, # joint corresponding authors