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Tzer Han Tan, Jifeng Liu, Anne Grapin-Botton
Mapping and exploring the organoid state space using synthetic biology.
Semin Cell Dev Biol, 141 23-32 (2023)
PubMed Source   

The functional relevance of an organoid is dependent on the differentiation, morphology, cell arrangement and biophysical properties, which collectively define the state of an organoid. For an organoid culture, an individual organoid or the cells that compose it, these state variables can be characterised, most easily by transcriptomics and by high-content image analysis. Their states can be compared to their in vivo counterparts. Current evidence suggests that organoids explore a wider state space than organs in vivo due to the lack of niche signalling and the variability of boundary conditions in vitro. Using data-driven state inference and in silico modelling, phase diagrams can be constructed to systematically sort organoids along biochemical or biophysical axes. These phase diagrams allow us to identify control strategies to modulate organoid state. To do so, the biochemical and biophysical environment, as well as the cells that seed organoids, can be manipulated.
@article{Tan8339,
author={Tzer Han Tan, Jifeng Liu, Anne Grapin-Botton},
title={Mapping and exploring the organoid state space using synthetic biology.},
journal ={Seminars in cell & developmental biology},
volume={141},
pages={23--32},
year=2023
}

Jane C Stinchcombe, Yukako Asano, Christopher J G Kaufman, Kristin Böhlig, Christopher J Peddie, Lucy M Collinson, André Nadler, Gillian M Griffiths
Ectocytosis renders T cell receptor signaling self-limiting at the immune synapse.
Science, 380(6647) 818-823 (2023)
PubMed Source   

Cytotoxic T lymphocytes (CTLs) kill virus-infected and cancer cells through T cell receptor (TCR) recognition. How CTLs terminate signaling and disengage to allow serial killing has remained a mystery. TCR activation triggers membrane specialization within the immune synapse, including the production of diacylglycerol (DAG), a lipid that can induce negative membrane curvature. We found that activated TCRs were shed into DAG-enriched ectosomes at the immune synapse rather than internalized through endocytosis, suggesting that DAG may contribute to the outward budding required for ectocytosis. Budding ectosomes were endocytosed directly by target cells, thereby terminating TCR signaling and simultaneously disengaging the CTL from the target cell to allow serial killing. Thus, ectocytosis renders TCR signaling self-limiting.
@article{Stinchcombe8550,
author={Jane C Stinchcombe, Yukako Asano, Christopher J G Kaufman, Kristin Böhlig, Christopher J Peddie, Lucy M Collinson, André Nadler, Gillian M Griffiths},
title={Ectocytosis renders T cell receptor signaling self-limiting at the immune synapse.},
journal ={Science (New York, N.Y.)},
volume={380},
issue ={6647},
pages={818--823},
year=2023
}

Ana P. Ramos, Alicja Szalapak, Lucrezia Camilla Ferme, Carl D. Modes
From Cells to Form: A Roadmap to study shape emergence in vivo.
Biophys J, Art. No. doi: 10.1016/j.bpj.2023.05.015 (2023)
Open Access PubMed Source   

Organogenesis arises from the collective arrangement of cells into progressively 3D-shaped tissue. The acquisition of a correctly shaped organ is then the result of a complex interplay between molecular cues, responsible for differentiation and patterning, and the mechanical properties of the system, which generate the necessary forces that drive correct shape emergence. Nowadays, technological advances in the fields of microscopy, molecular biology, and computer science are making it possible to see and record such complex interactions in incredible, unforeseen detail within the global context of the developing embryo. A quantitative and interdisciplinary perspective of developmental biology becomes then necessary for a comprehensive understanding of morphogenesis.
@article{Ramos8551,
author={Ana P. Ramos, Alicja Szalapak, Lucrezia Camilla Ferme, Carl D. Modes},
title={From Cells to Form: A Roadmap to study shape emergence in vivo.},
journal ={Biophysical journal},
volume={},
pages={1--1},
year=2023
}

Mateusz Susik, Ivo F. Sbalzarini
Variational inference accelerates accurate DNA mixture deconvolution.
Forensic Sci Int Genet, 65 Art. No. 102890 (2023)
Open Access   Source Full Text   

We investigate a class of DNA mixture deconvolution algorithms based on variational inference, and we show that this can significantly reduce computational runtimes with little or no effect on the accuracy and precision of the result. In particular, we consider Stein Variational Gradient Descent (SVGD) and Variational Inference (VI) with an evidence lower-bound objective. Both provide alternatives to the commonly used Markov-Chain Monte-Carlo methods for estimating the model posterior in Bayesian probabilistic genotyping. We demonstrate that both SVGD and VI significantly reduce computational costs over the current state of the art. Importantly, VI does so without sacrificing precision or accuracy, presenting an overall improvement over previously published methods.
@article{Susik8549,
author={Mateusz Susik, Ivo F. Sbalzarini},
title={Variational inference accelerates accurate DNA mixture deconvolution.},
journal ={Forensic science international. Genetics},
volume={65},
pages={null--null},
year=2023
}

Elisa Nerli#, Jenny Kretzschmar, Tommaso Bianucci, Mauricio Rocha-Martins, Christoph Zechner, Caren Norden#
Deterministic and probabilistic fate decisions co-exist in a single retinal lineage.
EMBO J, Art. No. doi: 10.15252/embj.2022112657 (2023)
PubMed Source Full Text   

Correct nervous system development depends on the timely differentiation of progenitor cells into neurons. While the output of progenitor differentiation is well investigated at the population and clonal level, how stereotypic or variable fate decisions are during development is still more elusive. To fill this gap, we here follow the fate outcome of single neurogenic progenitors in the zebrafish retina over time using live imaging. We find that neurogenic progenitor divisions produce two daughter cells, one of deterministic and one of probabilistic fate. Interference with the deterministic branch of the lineage affects lineage progression. In contrast, interference with fate probabilities of the probabilistic branch results in a broader range of fate possibilities than in wild-type and involves the production of any neuronal cell type even at non-canonical developmental stages. Combining the interference data with stochastic modelling of fate probabilities revealed that a simple gene regulatory network is able to predict the observed fate decision probabilities during wild-type development. These findings unveil unexpected lineage flexibility that could ensure robust development of the retina and other tissues.
@article{Nerli8546,
author={Elisa Nerli, Jenny Kretzschmar, Tommaso Bianucci, Mauricio Rocha-Martins, Christoph Zechner, Caren Norden},
title={Deterministic and probabilistic fate decisions co-exist in a single retinal lineage.},
journal ={The EMBO journal},
volume={},
pages={1--1},
year=2023
}

Tobias Boothe#, Mario Ivanković, Markus Grohme, M Andrea Markus, Christian Dullin, Xingbo Xu, Jochen Rink#
Content aware image restoration improves spatiotemporal resolution in luminescence imaging.
Commun Biol, 6(1) Art. No. 518 (2023)
Open Access PubMed Source   

Luminescent reporters are due to their intrinsically high signal-to-noise ratio a powerful labelling tool for microscopy and macroscopic in vivo imaging in biomedical research. However, luminescence signal detection requires longer exposure times than fluorescence imaging and is consequently less suited for applications requiring high temporal resolution or throughput. Here we demonstrate that content aware image restoration can drastically reduce the exposure time requirements in luminescence imaging, thus overcoming one of the major limitations of the technique.
@article{Boothe8552,
author={Tobias Boothe, Mario Ivanković, Markus Grohme, M Andrea Markus, Christian Dullin, Xingbo Xu, Jochen Rink},
title={Content aware image restoration improves spatiotemporal resolution in luminescence imaging.},
journal ={Communications biology},
volume={6},
issue ={1},
pages={null--null},
year=2023
}

Anupam Singh✳︎, Joan Antoni Soler Blasco✳︎, Janelle Lauer, Stephan W. Grill, Marcus Jahnel#, Marino Zerial#, Shashi Thutupalli#
Two-component molecular motor driven by a GTPase cycle.
Nat Phys, Art. No. doi: 10.1038/s41567-023-02009-3 (2023)
Open Access Source   

ATPases are a group of enzymes that can cyclically convert the free energy of ATP hydrolysis into mechanical work. GTPases are another class of enzymes that are predominantly associated with signal transduction processes, but their role in mechanotransduction is less established. It was previously shown that the binding of the GTPase Rab5 to the tethering protein EEA1 induces a large conformational change in EEA1 from a rigid, extended to a flexible, collapsed state. This entropic collapse of EEA1 gives rise to an effective force that can pull tethered membranes closer. It currently remains unclear if EEA1 can return from the collapsed to the extended conformation without the aid of chaperone proteins. Here we show that EEA1 in a bulk solution can undergo multiple flexibility transition cycles driven by the energetics of Rab5 binding and unbinding as well as GTP hydrolysis. Each cycle can perform up to 20kBT of mechanical work. Hence, Rab5 and EEA1 constitute a two-component molecular motor driven by the chemical energy derived from the Rab5 GTPase cycle. We conclude that tethering proteins and their small GTPase partners can have active mechanical roles in membrane trafficking.
@article{Singh8547,
author={Anupam Singh, Joan Antoni Soler Blasco, Janelle Lauer, Stephan W. Grill, Marcus Jahnel, Marino Zerial, Shashi Thutupalli},
title={Two-component molecular motor driven by a GTPase cycle.},
journal ={Nature physics},
volume={},
pages={1--1},
year=2023
}

Nicole S Paulat, Jessica M Storer, Diana D Moreno-Santillán, Austin B Osmanski, Kevin F. Sullivan, Jenna R Grimshaw, Jennifer M Korstian, Michaela Halsey, Carlos J Garcia, Claudia Crookshanks, Jaquelyn Roberts, Arian F A Smit, Robert Hubley, Jeb Rosen, Emma Teeling, Sonja Vernes, Eugene W Myers, Martin Pippel, Thomas Brown, Michael Hiller, Michael null, Danny Rojas, Liliana M Dávalos, Kerstin Lindblad-Toh, Elinor K Karlsson, David A Ray
Chiropterans Are a Hotspot for Horizontal Transfer of DNA Transposons in Mammalia.
Mol Biol Evol, 40(5) Art. No. msad092 (2023)
Open Access PubMed Source   

Horizontal transfer of transposable elements (TEs) is an important mechanism contributing to genetic diversity and innovation. Bats (order Chiroptera) have repeatedly been shown to experience horizontal transfer of TEs at what appears to be a high rate compared with other mammals. We investigated the occurrence of horizontally transferred (HT) DNA transposons involving bats. We found over 200 putative HT elements within bats; 16 transposons were shared across distantly related mammalian clades, and 2 other elements were shared with a fish and two lizard species. Our results indicate that bats are a hotspot for horizontal transfer of DNA transposons. These events broadly coincide with the diversification of several bat clades, supporting the hypothesis that DNA transposon invasions have contributed to genetic diversification of bats.
@article{Paulat8533,
author={Nicole S Paulat, Jessica M Storer, Diana D Moreno-Santillán, Austin B Osmanski, Kevin F. Sullivan, Jenna R Grimshaw, Jennifer M Korstian, Michaela Halsey, Carlos J Garcia, Claudia Crookshanks, Jaquelyn Roberts, Arian F A Smit, Robert Hubley, Jeb Rosen, Emma Teeling, Sonja Vernes, Eugene W Myers, Martin Pippel, Thomas Brown, Michael Hiller, Michael null, Danny Rojas, Liliana M Dávalos, Kerstin Lindblad-Toh, Elinor K Karlsson, David A Ray},
title={Chiropterans Are a Hotspot for Horizontal Transfer of DNA Transposons in Mammalia.},
journal ={Molecular biology and evolution},
volume={40},
issue ={5},
pages={null--null},
year=2023
}

Nadia Rostam, Soumyadeep Ghosh, Chi Fung Willis Chow, Anna Hadarovich, Cedric Landerer, Rajat Ghosh, HongKee Moon, Lena Hersemann, Diana M Mitrea, Isaac A Klein, Anthony Hyman, Agnes Toth-Petroczy
CD-CODE: crowdsourcing condensate database and encyclopedia.
Nat Methods, 20(5) 673-676 (2023)
Open Access PubMed Source   

The discovery of biomolecular condensates transformed our understanding of intracellular compartmentalization of molecules. To integrate interdisciplinary scientific knowledge about the function and composition of biomolecular condensates, we developed the crowdsourcing condensate database and encyclopedia ( cd-code.org ). CD-CODE is a community-editable platform, which includes a database of biomolecular condensates based on the literature, an encyclopedia of relevant scientific terms and a crowdsourcing web application. Our platform will accelerate the discovery and validation of biomolecular condensates, and facilitate efforts to understand their role in disease and as therapeutic targets.
@article{Rostam8520,
author={Nadia Rostam, Soumyadeep Ghosh, Chi Fung Willis Chow, Anna Hadarovich, Cedric Landerer, Rajat Ghosh, HongKee Moon, Lena Hersemann, Diana M Mitrea, Isaac A Klein, Anthony Hyman, Agnes Toth-Petroczy},
title={CD-CODE: crowdsourcing condensate database and encyclopedia.},
journal ={Nature methods},
volume={20},
issue ={5},
pages={673--676},
year=2023
}

Xiaojie Zhang✳︎, Sindhuja Sridharan✳︎, Ievgeniia Zagoriy, Christina Eugster Oegema, Cyan Ching, Tim Pflaesterer, Herman K H Fung, Isabelle Becher, Ina Poser, Christoph W Müller, Anthony Hyman, Mikhail M Savitski#, Julia Mahamid#
Molecular mechanisms of stress-induced reactivation in mumps virus condensates.
Cell, 186(9) 1877-1894 (2023)
Open Access PubMed Source   

Negative-stranded RNA viruses can establish long-term persistent infection in the form of large intracellular inclusions in the human host and cause chronic diseases. Here, we uncover how cellular stress disrupts the metastable host-virus equilibrium in persistent infection and induces viral replication in a culture model of mumps virus. Using a combination of cell biology, whole-cell proteomics, and cryo-electron tomography, we show that persistent viral replication factories are dynamic condensates and identify the largely disordered viral phosphoprotein as a driver of their assembly. Upon stress, increased phosphorylation of the phosphoprotein at its interaction interface with the viral polymerase coincides with the formation of a stable replication complex. By obtaining atomic models for the authentic mumps virus nucleocapsid, we elucidate a concomitant conformational change that exposes the viral genome to its replication machinery. These events constitute a stress-mediated switch within viral condensates that provide an environment to support upregulation of viral replication.
@article{Zhang8543,
author={Xiaojie Zhang, Sindhuja Sridharan, Ievgeniia Zagoriy, Christina Eugster Oegema, Cyan Ching, Tim Pflaesterer, Herman K H Fung, Isabelle Becher, Ina Poser, Christoph W Müller, Anthony Hyman, Mikhail M Savitski, Julia Mahamid},
title={Molecular mechanisms of stress-induced reactivation in mumps virus condensates.},
journal ={Cell},
volume={186},
issue ={9},
pages={1877--1894},
year=2023
}
✳︎ joint first authors, # joint corresponding authors
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