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Luis David Garcia Puente, Elizabeth Gross, Heather A Harrington, Matthew Johnston, Nicolette Meshkat, Mercedes Perez Millan, Anne Shiu
Absolute concentration robustness: Algebra and geometry.
J SYMB COMPUT, 128 Art. No. 102398 (2025)
Open Access Source   

Motivated by the question of how biological systems maintain homeostasis in changing environments, Shinar and Feinberg introduced in 2010 the concept of absolute concentration robustness (ACR). A biochemical system exhibits ACR in some species if the steady-state value of that species does not depend on initial conditions. Thus, a system with ACR can maintain a constant level of one species even as the initial condition changes. Despite a great deal of interest in ACR in recent years, the following basic question remains open: How can we determine quickly whether a given biochemical system has ACR? Although various approaches to this problem have been proposed, we show that they are incomplete. Accordingly, we present new methods for deciding ACR, which harness computational algebra. We illustrate our results on several biochemical signaling networks.
@article{Puente8861,
author={Luis David Garcia Puente, Elizabeth Gross, Heather A Harrington, Matthew Johnston, Nicolette Meshkat, Mercedes Perez Millan, Anne Shiu},
title={Absolute concentration robustness: Algebra and geometry.},
journal ={Journal of Symbolic Computation },
volume={128},
pages={1--1},
year=2025
}

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
}

Henry Carey-Morgan, Nabarun Polley, Till Korten, Claudia Pacholski, Stefan Diez
Microscope-Free Analyte Detection Based on Fiber-Optic Gliding Motility Assays.
Small, Art. No. doi: 10.1002/smll.202411836 (2025)
Open Access PubMed Source   

Prolonged hospital waiting times are linked with increased patient mortality and cause additional financial burdens on institutions. Efficient point-of-care diagnosis would help alleviate this, but is hampered by a lack of cost-effective devices capable of rapid, in situ, wide ranging analyte detection. Lab-on-fiber technology provides an answer allowing for diagnosis, treatment, and monitoring in situ with real time feedback. Here, a device is demonstrated that harnesses motor-protein-driven-microtubule molecular detection assays to optical fibers. By developing a new method for microscope-free microtubule gliding speed determination, proof of concept is demonstrated in the detection of Monomeric Streptavidin and Neutravidin, which initiate a decrease in speed in biotinylated microtubules as well as bundling in the latter case. Utilizing antibody functionalizsed microtubules label-free and microscope-free detection of the heart attack marker Creatine Kinase-MB, as well secondary antibodies in nm concentration is demonstrated. This detector has the potential to be used in situ, providing rapid, low-cost, multiplex analyte screening and detection.
@article{Carey-Morgan8973,
author={Henry Carey-Morgan, Nabarun Polley, Till Korten, Claudia Pacholski, Stefan Diez},
title={Microscope-Free Analyte Detection Based on Fiber-Optic Gliding Motility Assays.},
journal ={Small (Weinheim an der Bergstrasse, Germany)},
volume={},
pages={1--1},
year=2025
}

Federica Luppino, Swantje Lenz, Chi Fung Willis Chow, Agnes Toth-Petroczy
Deep learning tools predict variants in disordered regions with lower sensitivity.
BMC Genomics, 26(1) 367-367 (2025)
Open Access PubMed Source   

The recent AI breakthrough of AlphaFold2 has revolutionized 3D protein structural modeling, proving crucial for protein design and variant effects prediction. However, intrinsically disordered regions-known for their lack of well-defined structure and lower sequence conservation-often yield low-confidence models. The latest Variant Effect Predictor (VEP), AlphaMissense, leverages AlphaFold2 models, achieving over 90% sensitivity and specificity in predicting variant effects. However, the effectiveness of tools for variants in disordered regions, which account for 30% of the human proteome, remains unclear.
@article{Luppino8950,
author={Federica Luppino, Swantje Lenz, Chi Fung Willis Chow, Agnes Toth-Petroczy},
title={Deep learning tools predict variants in disordered regions with lower sensitivity.},
journal ={BMC genomics},
volume={26},
issue ={1},
pages={367--367},
year=2025
}

Alba Villaronga-Luque*, Ryan Savill*, Natalia López-Anguita, Adriano Bolondi, Sumit Garai, Seher Ipek Gassaloglu, Roua Rouatbi, Kathrin Schmeisser, Aayush Poddar, Lisa Bauer, Tiago Alves, Sofia Traikov, Jonathan Rodenfels, Trian Chavakis, Aydan Bulut-Karslioglu, Jesse V Veenvliet
Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model.
Cell Stem Cell, Art. No. doi: 10.1016/j.stem.2025.03.012 (2025)
Open Access PubMed Source   

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic variation remain unclear. Here, we investigated the roots of phenotypic variation by parallel recording of transcriptomic states and morphological history in individual structures modeling embryonic trunk formation. Machine learning and integration of time-resolved single-cell RNA sequencing with imaging-based phenotypic profiling identified early features predictive of phenotypic end states. Leveraging this predictive power revealed that early imbalance of oxidative phosphorylation and glycolysis results in aberrant morphology and a neural lineage bias, which we confirmed by metabolic measurements. Accordingly, metabolic interventions improved phenotypic end states. Collectively, our work establishes divergent metabolic states as drivers of phenotypic variation and offers a broadly applicable framework to chart and predict phenotypic variation in organoids and SEMs. The strategy can be used to identify and control underlying biological processes, ultimately increasing reproducibility.
@article{Villaronga-Luque8970,
author={Alba Villaronga-Luque, Ryan Savill, Natalia López-Anguita, Adriano Bolondi, Sumit Garai, Seher Ipek Gassaloglu, Roua Rouatbi, Kathrin Schmeisser, Aayush Poddar, Lisa Bauer, Tiago Alves, Sofia Traikov, Jonathan Rodenfels, Trian Chavakis, Aydan Bulut-Karslioglu, Jesse V Veenvliet},
title={Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model.},
journal ={Cell stem cell},
volume={},
pages={1--1},
year=2025
}

Kristina S Stapornwongkul#, Elisa Hahn, Patryk Poliński, Laura Salamó Palau, Krisztina Arató, LiAng Yao, Kate Williamson, Nicola Gritti, Kerim Anlas, Mireia Osuna Lopez, Kiran R Patil, Idse Heemskerk, Miki Ebisuya#, Vikas Trivedi#
Glycolytic activity instructs germ layer proportions through regulation of Nodal and Wnt signaling.
Cell Stem Cell, Art. No. doi: 10.1016/j.stem.2025.03.011 (2025)
Open Access PubMed Source   

Metabolic pathways can influence cell fate decisions, yet their regulative role during embryonic development remains poorly understood. Here, we demonstrate an instructive role of glycolytic activity in regulating signaling pathways involved in mesoderm and endoderm specification. Using a mouse embryonic stem cell (mESC)-based in vitro model for gastrulation, we found that glycolysis inhibition increases ectodermal cell fates at the expense of mesodermal and endodermal lineages. We demonstrate that this relationship is dose dependent, enabling metabolic control of germ layer proportions through exogenous glucose levels. We further show that glycolysis acts as an upstream regulator of Nodal and Wnt signaling and that its influence on cell fate specification can be decoupled from its effects on growth. Finally, we confirm the generality of our findings using a human gastrulation model. Our work underscores the dependence of signaling pathways on metabolic conditions and provides mechanistic insight into the nutritional regulation of cell fate decision-making.
@article{Stapornwongkul8972,
author={Kristina S Stapornwongkul, Elisa Hahn, Patryk Poliński, Laura Salamó Palau, Krisztina Arató, LiAng Yao, Kate Williamson, Nicola Gritti, Kerim Anlas, Mireia Osuna Lopez, Kiran R Patil, Idse Heemskerk, Miki Ebisuya, Vikas Trivedi},
title={Glycolytic activity instructs germ layer proportions through regulation of Nodal and Wnt signaling.},
journal ={Cell stem cell},
volume={},
pages={1--1},
year=2025
}

Alexandra A Baumann*, Lisanne I Knol*, Marie Arlt, Tim Hutschenreiter, Anja Richter, Thomas Widmann, Marcus Franke, Karl Hackmann, Sylke Winkler, Daniela Richter, Isabel Spier, Stefan Aretz, Daniela Aust, Joseph Porrmann, Doreen William, Evelin Schröck, Hanno Glimm, Arne Jahn
Long-read genome and RNA sequencing resolve a pathogenic intronic germline LINE-1 insertion in APC.
NPJ Genom Med, 10(1) Art. No. 30 (2025)
Open Access PubMed Source Full Text   

Familial adenomatous polyposis (FAP) is caused by pathogenic germline variants in the tumor suppressor gene APC. Confirmation of diagnosis was not achieved by cancer gene panel and exome sequencing or custom array-CGH in a family with suspected FAP across five generations. Long-read genome sequencing (PacBio), short-read genome sequencing (Illumina), short-read RNA sequencing, and further validations were performed in different tissues of multiple family members. Long-read genome sequencing resolved a 6 kb full-length intronic insertion of a heterozygous LINE-1 element between exons 7 and 8 of APC that could be detected but not fully resolved by short-read genome sequencing. Targeted RNA analysis revealed aberrant splicing resulting in the formation of a pseudo-exon with a premature stop codon. The variant segregated with the phenotype in several family members allowing its evaluation as likely pathogenic. This study supports the utility of long-read DNA sequencing and complementary RNA approaches to tackle unsolved cases of hereditary disease.
@article{Baumann8943,
author={Alexandra A Baumann, Lisanne I Knol, Marie Arlt, Tim Hutschenreiter, Anja Richter, Thomas Widmann, Marcus Franke, Karl Hackmann, Sylke Winkler, Daniela Richter, Isabel Spier, Stefan Aretz, Daniela Aust, Joseph Porrmann, Doreen William, Evelin Schröck, Hanno Glimm, Arne Jahn},
title={Long-read genome and RNA sequencing resolve a pathogenic intronic germline LINE-1 insertion in APC.},
journal ={NPJ genomic medicine},
volume={10},
issue ={1},
pages={null--null},
year=2025
}

Rachele Catalano, Y Zhao, M Pecak, T Korten#, S Diez#
Barcoding Microtubules: Encoding Information onto Macromolecules by Photobleaching.
Nano Lett, 25(13) 5283-5290 (2025)
Open Access PubMed Source   

Kinesin-1-powered microtubules have emerged as versatile components in biocomputing and biosensing technologies. However, the inability to identify and track individual microtubules has constrained their applications to ensemble behaviors, limiting their potential for single-entity-based nanotechnologies. To address this challenge, we present a novel method for encoding digital information directly onto individual microtubules using photobleaching patterns. Binary numbers (1 to 15) were encoded within ∼12 μm segments of moving microtubules by photobleaching with a stationary pulsed laser, creating spatial frequency patterns corresponding to distinct bits of information. Fourier analysis enabled the accurate retrieval of the encoded data, demonstrating the feasibility of direct information storage and retrieval on macromolecular structures. This approach offers a transformative solution for recording microtubule trajectories within nanotechnological devices by encoding path information directly onto microtubules at branch points, obviating the need for video-based tracking. We anticipate that this innovation will advance the development of individualized microtubule-based technologies.
@article{Catalano8936,
author={Rachele Catalano, Y Zhao, M Pecak, T Korten, S Diez},
title={Barcoding Microtubules: Encoding Information onto Macromolecules by Photobleaching.},
journal ={Nano letters},
volume={25},
issue ={13},
pages={5283--5290},
year=2025
}

Chi Fung Willis Chow*, Swantje Lenz*, Maxim Scheremetjew, Soumyadeep Ghosh, Doris Richter, Ceciel Jegers, Alexander von Appen, Simon Alberti, Agnes Toth-Petroczy
SHARK-capture identifies functional motifs in intrinsically disordered protein regions.
Protein Sci, 34(4) Art. No. e70091 (2025)
Open Access PubMed Source   

Increasing insights into how sequence motifs in intrinsically disordered regions (IDRs) provide functions underscore the need for systematic motif detection. Contrary to structured regions where motifs can be readily identified from sequence alignments, the rapid evolution of IDRs limits the usage of alignment-based tools in reliably detecting motifs within. Here, we developed SHARK-capture, an alignment-free motif detection tool designed for difficult-to-align regions. SHARK-capture innovates on word-based methods by flexibly incorporating amino acid physicochemistry to assess motif similarity without requiring rigid definitions of equivalency groups. SHARK-capture offers consistently strong performance in a systematic benchmark, with superior residue-level performance. SHARK-capture identified known functional motifs across orthologs of the microtubule-associated zinc finger protein BuGZ. We also identified a short motif in the IDR of S. cerevisiae RNA helicase Ded1p, which we experimentally verified to be capable of promoting ATPase activity. Our improved performance allows us to systematically calculate 10,889 motifs for 2695 yeast IDRs and provide it as a resource. SHARK-capture offers the most precise tool yet for the systematic identification of conserved regions in IDRs and is freely available as a Python package (https://pypi.org/project/bio-shark/) and on https://git.mpi-cbg.de/tothpetroczylab/shark.
@article{Chow8938,
author={Chi Fung Willis Chow, Swantje Lenz, Maxim Scheremetjew, Soumyadeep Ghosh, Doris Richter, Ceciel Jegers, Alexander von Appen, Simon Alberti, Agnes Toth-Petroczy},
title={SHARK-capture identifies functional motifs in intrinsically disordered protein regions.},
journal ={Protein science : a publication of the Protein Society},
volume={34},
issue ={4},
pages={null--null},
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
}
* joint first authors, # joint corresponding authors