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Woorin Kim#, Nicola Schmidt, Matthias Jost, Elijah Mbandi Mkala, Sylke Winkler, Guangwan Hu, Tony Heitkam#, Stefan Wanke#
Diverging repeatomes in holoparasitic Hydnoraceae uncover a playground of genome evolution.
New Phytol, 247(3) 1520-1537 (2025)
Open Access PubMed Source   

The transition from an autotrophic to a heterotrophic lifestyle is associated with numerous genomic changes. These often involve large genomic alterations, potentially driven by repetitive DNAs. Despite their recognized role in shaping plant genomes, the contribution of repetitive DNAs to parasitic plant genome evolution remains largely unexplored. This study presents the first analysis of repetitive DNAs in Hydnoraceae genomes, a plant family whose members are holoparasitic. Repetitive DNAs were identified and annotated de novo. Abundant transposable elements and 35S ribosomal DNA in the Hydnora visseri genome were reconstructed in silico. Their patterns of abundance and presence-absence were individually and comparatively analyzed. Both Hydnoraceae genera, Hydnora and Prosopanche, exhibit distinct repeatome profiles which challenge our current understanding of repeatome and rDNA evolution. The Hydnora genomes are dominated by long terminal repeat retrotransposons, while the Prosopanche genomes vary greatly in their repeat composition: Prosopanche bonacinae with a highly abundant single DNA transposon and Prosopanche panguanensis with over 15% 5S rDNA, compared to ≤ 0.1% in the Hydnora genomes. The repeat profiles align with the phylogeny, geographical distribution, and host shifts of the Hydnoraceae, indicating a potential role of repetitive DNAs in shaping Hydnoraceae genomes to adapt to the parasitic lifestyle.
@article{Kim9014,
author={Woorin Kim, Nicola Schmidt, Matthias Jost, Elijah Mbandi Mkala, Sylke Winkler, Guangwan Hu, Tony Heitkam, Stefan Wanke},
title={Diverging repeatomes in holoparasitic Hydnoraceae uncover a playground of genome evolution.},
journal ={The New phytologist},
volume={247},
issue ={3},
pages={1520--1537},
year=2025
}

Angus Inman, Elisabeth Spiritosanto, Bridget L Evans, Judith E Lutton, Masazumi Tada, Till Bretschneider, Pierre A. Haas#, Michael Smutny#
A multi-tiered mechanical mechanism shapes the early neural plate.
Nat Commun, 16(1) Art. No. 6187 (2025)
Open Access PubMed Source   

The formation of complex tissues during embryonic development requires an intricate spatiotemporal coordination of local mechanical processes regulating global tissue morphogenesis. Here, we uncover a novel mechanism that mechanically regulates the shape of the anterior neural plate (ANP), a vital forebrain precursor, during zebrafish gastrulation. Combining in vivo and in silico approaches we reveal that the ANP is shaped by global tissue flows regulated by distinct force-generating processes. We show that mesendoderm migration and E-cadherin-dependent differential tissue interactions control distinct flow regimes in the neuroectoderm. Initial opposing flows lead to neuroectoderm cell internalisation and progressive multilayer tissue folding which in turn provide forces driving ANP tissue reshaping. We find that convergent extension is dispensable for internalisation but required for ANP tissue extension. Our results highlight how spatiotemporal regulation and coupling of different mechanical processes between tissues in the embryo control the first internalisation and folding events of the developing brain.
@article{Inman9020,
author={Angus Inman, Elisabeth Spiritosanto, Bridget L Evans, Judith E Lutton, Masazumi Tada, Till Bretschneider, Pierre A. Haas, Michael Smutny},
title={A multi-tiered mechanical mechanism shapes the early neural plate.},
journal ={Nature communications},
volume={16},
issue ={1},
pages={null--null},
year=2025
}

Theresia Gutmann*#, David Kuster*, Anthony Hyman#
SARS-CoV-2 nucleocapsid protein directly prevents cGAS-DNA recognition through competitive binding.
Proc Natl Acad Sci U.S.A., 122(26) Art. No. doi: 10.1073/pnas.2426204122 (2025)
Open Access PubMed Source   

A hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the delayed interferon response. Interferons are typically produced upon host recognition of pathogen- or damage-associated molecular patterns, such as nucleic acids. While the mechanisms by which SARS-CoV-2 evades host recognition of its RNA are well studied, how it evades immune responses to cytosolic DNA-leaked from mitochondria or nuclei during infection-remains poorly understood. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein directly suppresses DNA sensing by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS). Although primarily known for packaging the viral RNA genome, we uncover that the SARS-CoV-2 nucleocapsid protein also binds DNA with high affinity and competitively blocks cGAS activation. Using cell-free biochemical and biophysical approaches, including single-molecule optical tweezers, we show that the nucleocapsid protein binds to DNA at nanomolar concentrations and cocondenses with DNA at micromolar concentrations, thereby impeding stable cGAS-DNA interactions required for signal propagation. Hyperphosphorylation of the nucleocapsid protein diminishes its competitive binding capacity. Our findings reveal an unexpected role of the SARS-CoV-2 nucleocapsid protein in directly suppressing the cGAS-STING pathway, strongly suggesting that this contributes to the delayed interferon response during infection. This study raises the possibility that nucleocapsid proteins of other RNA viruses may also exhibit moonlighting functions by antagonizing host nucleic acid-sensing pathways.
@article{Gutmann9017,
author={Theresia Gutmann, David Kuster, Anthony Hyman},
title={SARS-CoV-2 nucleocapsid protein directly prevents cGAS-DNA recognition through competitive binding.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={122},
issue ={26},
pages={1--1},
year=2025
}

Esteban Quezada, Klaus-Peter Knoch, Jovana Vasiljevic, Annika Seiler, Akshaye Pal, Abishek Gunasekaran, Carla Münster, Daniela Friedland, Eyke Schöniger, Anke Sönmez, Pascal Roch, Carolin Wegbrod, Katharina Ganß, Nicole Kipke, Simon Alberti, Rita Nano, Lorenzo Piemonti, Daniela Aust, Jürgen Weitz, Marius Distler, Michele Solimena
Aldolase-regulated G3BP1/2+ condensates control insulin mRNA storage in beta cells.
EMBO J, 44(13) 3669-3696 (2025)
Open Access PubMed Source   

Upregulation of insulin mRNA translation upon hyperglycemia in pancreatic islet β-cells involves several RNA-binding proteins. Here, we found that G3BP1, a stress granule marker downregulated in islets of subjects with type 2 diabetes, binds to insulin mRNA in glucose concentration-dependent manner. We show in mouse insulinoma MIN6-K8 cells exposed to fasting glucose levels that G3BP1 and its paralog G3BP2 colocalize to cytosolic condensates with eIF3b, phospho-AMPKαThr172 and Ins1/2 mRNA. Glucose stimulation dissolves G3BP1+/2+ condensates with cytosolic redistribution of their components. The aldolase inhibitor aldometanib prevents the glucose- and pyruvate-induced dissolution of G3BP1+/2+ condensates, increases phospho-AMPKαThr172 levels and reduces those of phospho-mTORSer2448. G3BP1 or G3BP2 depletion precludes condensate assembly. KO of G3BP1 decreases Ins1/2 mRNA abundance and translation as well as proinsulin levels, and impaires glucose-stimulated insulin secretion. Further, other insulin secretagogues such as exendin-4 and palmitate, but not high KCl, prompts the dissolution of G3BP1+/2+ condensates. G3BP1+/2+/Ins mRNA+ condensates are also found in primary mouse and human β-cells. Hence, G3BP1+/2+ condensates represent a conserved glycolysis/aldolase-regulated compartment for the physiological storage and protection of insulin mRNA in resting β-cells.
@article{Quezada9001,
author={Esteban Quezada, Klaus-Peter Knoch, Jovana Vasiljevic, Annika Seiler, Akshaye Pal, Abishek Gunasekaran, Carla Münster, Daniela Friedland, Eyke Schöniger, Anke Sönmez, Pascal Roch, Carolin Wegbrod, Katharina Ganß, Nicole Kipke, Simon Alberti, Rita Nano, Lorenzo Piemonti, Daniela Aust, Jürgen Weitz, Marius Distler, Michele Solimena},
title={Aldolase-regulated G3BP1/2+ condensates control insulin mRNA storage in beta cells.},
journal ={The EMBO journal},
volume={44},
issue ={13},
pages={3669--3696},
year=2025
}

Justina Stark#, Rohit Krishnan Harish, Ivo F. Sbalzarini, Michael Brand#
Morphogen gradients are regulated by porous media characteristics of the developing tissue.
Development, 152(13) Art. No. dev204312 (2025)
Open Access PubMed Source   

Long-range morphogen gradients have been proposed to form by morphogen diffusion from a localized source to distributed sinks in the target tissue. The role of the complex tissue geometry in this process is, however, less well understood and has not been explicitly resolved in existing models. Here, we numerically reconstruct pore-scale 3D geometries of zebrafish epiboly from light-sheet microscopy volumes. In these high-resolution 3D geometries, we simulate Fgf8a gradient formation in the tortuous extracellular space. Our simulations show that when realistic embryo geometries are considered, a source-diffusion-degradation mechanism with additional binding to extracellular matrix polymers is sufficient to explain emergence and robust maintenance of Fgf8a gradients. The predicted normalized gradient is robust against changes in source and sink rates but sensitive to changes in the pore connectivity of the extracellular space, with lower connectivity leading to steeper and shorter gradients. This demonstrates the importance of considering realistic geometries when studying morphogen gradients.
@article{Stark9009,
author={Justina Stark, Rohit Krishnan Harish, Ivo F. Sbalzarini, Michael Brand},
title={Morphogen gradients are regulated by porous media characteristics of the developing tissue.},
journal ={Development (Cambridge, England)},
volume={152},
issue ={13},
pages={null--null},
year=2025
}

Xinyi Yang, Teresa Ferraro, Kelly Molnar, Julien Pontabry, Sam-Rayden Malanda, Nicola Maghelli, Loic Royer, Stephan W. Grill, Gene Myers, Silvia Grigolon, Michel Labouesse
Repeated extrinsic and anisotropic mechanical inputs promote C. elegans polarized adherens junction elongation.
Dev Cell, Art. No. doi: 10.1016/j.devcel.2025.06.012 (2025)
Open Access PubMed Source   

A key challenge in development is understanding how complex organisms physically coordinate the morphogenesis of multiple tissues. Here, using biophysical approaches, we investigate how muscles under the epidermis specifically stimulate the extension of anterior-posterior (AP)-oriented epidermal adherens junctions during late C. elegans embryonic elongation. First, light-sheet imaging shows that asynchronous patterns of muscle contractions drive embryo rotations. In turn, junctions between the lateral and dorso-ventral epidermis repeatedly oscillate between a folded, hypotensed state and an extended, hypertensed state. Second, fluorescence recovery after photobleaching (FRAP) analysis of an E-cadherin::GFP construct shows that muscle contractions stimulate E-cadherin turnover. Moreover, a mechano-chemical model backed by genetic tests suggests that E-cadherin trafficking controls junction elongation due to lower line tension. Altogether, our results illustrate how muscle contractions fluidize epidermal adherens junctions, which, combined with anisotropic tension in the epidermis, drive their polarized extension.
@article{Yang9021,
author={Xinyi Yang, Teresa Ferraro, Kelly Molnar, Julien Pontabry, Sam-Rayden Malanda, Nicola Maghelli, Loic Royer, Stephan W. Grill, Gene Myers, Silvia Grigolon, Michel Labouesse},
title={Repeated extrinsic and anisotropic mechanical inputs promote C. elegans polarized adherens junction elongation.},
journal ={Developmental cell},
volume={},
pages={1--1},
year=2025
}

Yaqing Zhang#, Yuan Jiang, David Kuster, Qiwei Ye, Wenhao Huang, Simon Fürbacher, Jingye Zhang, Pia Doll, Wenjun Lin, Siwei Dong, Hui Wang, Zhipeng Tang, David Ibberson, Klemens Wild, Irmgard Sinning, Anthony Hyman, Andres Jäschke#
Single-step discovery of high-affinity RNA ligands by UltraSelex.
Nat Chem Biol, 21(7) 1118-1126 (2025)
PubMed Source Full Text   

Aptamers, nucleic acid ligands targeting specific molecules, have emerged as drug candidates, sensors, imaging tools and nanotechnology building blocks. The predominant method for their discovery, systematic evolution of ligands by exponential enrichment, while successful, is laborious, time-consuming and often results in candidates enriched for unintended criteria. Here we present UltraSelex, a noniterative method that combines biochemical partitioning, high-throughput sequencing and computational signal-to-background rank modeling for discovering RNA aptamers in about 1 day. UltraSelex identified high-affinity RNA aptamers capable of binding a fluorogenic silicon rhodamine dye and two protein targets, the SARS-CoV-2 RNA-dependent RNA polymerase and HIV reverse transcriptase, enabling live-cell RNA imaging and efficient enzyme inhibition, respectively. From the ranked sequences, minimal aptamer motifs could be easily inferred. UltraSelex provides a rapid route to reveal new drug candidates and diagnostic tools.
@article{Zhang8945,
author={Yaqing Zhang, Yuan Jiang, David Kuster, Qiwei Ye, Wenhao Huang, Simon Fürbacher, Jingye Zhang, Pia Doll, Wenjun Lin, Siwei Dong, Hui Wang, Zhipeng Tang, David Ibberson, Klemens Wild, Irmgard Sinning, Anthony Hyman, Andres Jäschke},
title={Single-step discovery of high-affinity RNA ligands by UltraSelex.},
journal ={Nature chemical biology},
volume={21},
issue ={7},
pages={1118--1126},
year=2025
}

Yu Meng, Szabolcs Horvát, Carl D. Modes, Pierre A. Haas
Impossible ecologies: Interaction networks and stability of coexistence in ecological communities.
Cell Syst, Art. No. doi: 10.1016/j.cels.2025.101297 (2025)
Open Access PubMed Source   

Does an ecological community allow stable species coexistence? Identifying the general effects of competitive, mutualistic, and predator-prey interactions on stability remains a central problem of systems ecology because established approaches cannot account for the full network arrangement of these interactions. Here, we therefore analyze all interaction networks of N≤5 species with Lotka-Volterra dynamics by combining exact results and numerical exploration. We find that a very small subset of these networks is "impossible ecologies," in which stable coexistence is non-trivially impossible. We prove that the possibility of stable coexistence is determined by similarly rare "irreducible ecologies." Statistical sampling shows that this probability varies over orders of magnitude even in ecologies that differ only in the network arrangement of identical interactions. Thus, our approach reveals that the full network structure of interactions can influence stability of coexistence more than the established effect of interaction-type proportions. A record of this paper's transparent peer review process is included in the supplemental information.
@article{Meng9018,
author={Yu Meng, Szabolcs Horvát, Carl D. Modes, Pierre A. Haas},
title={Impossible ecologies: Interaction networks and stability of coexistence in ecological communities.},
journal ={Cell systems},
volume={},
pages={null--null},
year=2025
}

Shiheng Zhao, Pierre A. Haas
Mechanics of Poking a Cyst.
Phys Rev Lett, 134(22) Art. No. 228402 (2025)
Open Access PubMed Source   

Indentation tests are classical tools to determine material properties. For biological samples such as cysts of cells, however, the observed force-displacement relation cannot be expected to follow predictions for simple materials. Here, by solving the Pogorelov problem of a point force indenting an elastic shell for a purely nonlinear material, we discover that complex material behavior can even give rise to new scaling exponents in this force-displacement relation. In finite-element simulations, we show that these exponents are surprisingly robust, persisting even for thick shells indented with a sphere. By scaling arguments, we generalize our results to pressurized and prestressed shells, uncovering additional new scaling exponents. We find these predicted scaling exponents in the force-displacement relation observed in cyst indentation experiments. Our results thus form the basis for inferring the mechanisms that set the mechanical properties of these biological materials.
@article{Zhao9019,
author={Shiheng Zhao, Pierre A. Haas},
title={Mechanics of Poking a Cyst.},
journal ={Physical review letters},
volume={134},
issue ={22},
pages={null--null},
year=2025
}

Matthias Höllerhage*, Linghan Duan*, Oscar Wing Ho Chua, Claudia Moebius, Svenja H Bothe, Kristina Losse, Rebecca Kotzur, Kristina Lau, Franziska Hopfner, Franziska Richter, Christian Wahl-Schott, Marc Bickle, Günter U Höglinger
A genome-wide RNA interference screening reveals protectiveness of SNX5 knockdown in a Parkinson's disease cell model.
Transl Neurodegener, 14(1) Art. No. 27 (2025)
Open Access PubMed Source   

Alpha-synuclein (αSyn) is a major player in the pathophysiology of synucleinopathies, which include Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. To date, there is no disease-modifying therapy available for these synucleinopathies. Furthermore, the intracellular mechanisms by which αSyn confers toxicity are not yet fully understood. Therefore, it is of utmost importance to investigate the pathophysiology of αSyn-induced toxicity in order to identify novel molecular targets for the development of disease-modifying therapies.
@article{Höllerhage9010,
author={Matthias Höllerhage, Linghan Duan, Oscar Wing Ho Chua, Claudia Moebius, Svenja H Bothe, Kristina Losse, Rebecca Kotzur, Kristina Lau, Franziska Hopfner, Franziska Richter, Christian Wahl-Schott, Marc Bickle, Günter U Höglinger},
title={A genome-wide RNA interference screening reveals protectiveness of SNX5 knockdown in a Parkinson's disease cell model.},
journal ={Translational neurodegeneration},
volume={14},
issue ={1},
pages={null--null},
year=2025
}
* joint first authors, # joint corresponding authors