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Maximilian Driller, Thomas Brown, Shannon E Currie, Michael Hiller, Sylke Winkler, Martin Pippel, Christian C Voigt, Jörns Fickel, Camila J Mazzoni
A haplotype-resolved reference genome of a long-distance migratory bat, Pipistrellus nathusii (Keyserling & Blasius, 1839).
DNA Res, 31(4) Art. No. dsae018 (2024)
Open Access PubMed Source   

We present a complete, chromosome-scale reference genome for the long-distance migratory bat Pipistrellus nathusii. The genome encompasses both haplotypic sets of autosomes and the separation of both sex chromosomes by utilizing highly accurate long-reads and preserving long-range phasing information through the use of three-dimensional chromatin conformation capture sequencing (Hi-C). This genome, accompanied by a comprehensive protein-coding sequence annotation, provides a valuable genomic resource for future investigations into the genomic bases of long-distance migratory flight in bats as well as uncovering the genetic architecture, population structure and evolutionary history of Pipistrellus nathusii. The reference-quality genome presented here gives a fundamental resource to further our understanding of bat genetics and evolution, adding to the growing number of high-quality genetic resources in this field. Here, we demonstrate its use in the phylogenetic reconstruction of the order Chiroptera, and in particular, we present the resources to allow detailed investigations into the genetic drivers and adaptations related to long-distance migration.
@article{Driller8726,
author={Maximilian Driller, Thomas Brown, Shannon E Currie, Michael Hiller, Sylke Winkler, Martin Pippel, Christian C Voigt, Jörns Fickel, Camila J Mazzoni},
title={A haplotype-resolved reference genome of a long-distance migratory bat, Pipistrellus nathusii (Keyserling & Blasius, 1839).},
journal ={DNA research : an international journal for rapid publication of reports on genes and genomes},
volume={31},
issue ={4},
pages={null--null},
year=2024
}

Arun Pal, Dajana Grossmann, Hannes Glaß, Vitaly Zimyanin, René Günther, Marica Catinozzi, Tobias M Boeckers, Jared Sterneckert, Erik Storkebaum, Susanne Petri, Florian Wegner, Stephan W. Grill, Francisco Pan-Montojo#, Andreas Hermann#
Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS - and SOD1-ALS.
Life Sci Alliance, 7(8) Art. No. e202302535 (2024)
Open Access PubMed Source   

Amyotrophic lateral sclerosis (ALS) leads to death within 2-5 yr. Currently, available drugs only slightly prolong survival. We present novel insights into the pathophysiology of Superoxide Dismutase 1 (SOD1)- and in particular Fused In Sarcoma (FUS)-ALS by revealing a supposedly central role of glycolic acid (GA) and D-lactic acid (DL)-both putative products of the Parkinson's disease associated glyoxylase DJ-1. Combined, not single, treatment with GA/DL restored axonal organelle phenotypes of mitochondria and lysosomes in FUS- and SOD1-ALS patient-derived motoneurons (MNs). This was not only accompanied by restoration of mitochondrial membrane potential but even dependent on it. Despite presenting an axonal transport deficiency as well, TDP43 patient-derived MNs did not share mitochondrial depolarization and did not respond to GA/DL treatment. GA and DL also restored cytoplasmic mislocalization of FUS and FUS recruitment to DNA damage sites, recently reported being upstream of the mitochondrial phenotypes in FUS-ALS. Whereas these data point towards the necessity of individualized (gene-) specific therapy stratification, it also suggests common therapeutic targets across different neurodegenerative diseases characterized by mitochondrial depolarization.
@article{Pal8722,
author={Arun Pal, Dajana Grossmann, Hannes Glaß, Vitaly Zimyanin, René Günther, Marica Catinozzi, Tobias M Boeckers, Jared Sterneckert, Erik Storkebaum, Susanne Petri, Florian Wegner, Stephan W. Grill, Francisco Pan-Montojo, Andreas Hermann},
title={Glycolic acid and D-lactate-putative products of DJ-1-restore neurodegeneration in FUS - and SOD1-ALS.},
journal ={Life science alliance},
volume={7},
issue ={8},
pages={null--null},
year=2024
}

Nicolás Bettancourt, Cristian Pérez-Gallardo, Valeria Candia, Pamela Guevara, Yannis Kalaidzidis, Marino Zerial, Fabián Segovia-Miranda#, Hernán Morales-Navarrete#
Virtual tissue microstructure reconstruction across species using generative deep learning.
PLoS ONE, 19(7) Art. No. e0306073 (2024)
Open Access PubMed Source Full Text   

Analyzing tissue microstructure is essential for understanding complex biological systems in different species. Tissue functions largely depend on their intrinsic tissue architecture. Therefore, studying the three-dimensional (3D) microstructure of tissues, such as the liver, is particularly fascinating due to its conserved essential roles in metabolic processes and detoxification. Here, we present TiMiGNet, a novel deep learning approach for virtual 3D tissue microstructure reconstruction using Generative Adversarial Networks and fluorescence microscopy. TiMiGNet overcomes challenges such as poor antibody penetration and time-intensive procedures by generating accurate, high-resolution predictions of tissue components across large volumes without the need of paired images as input. We applied TiMiGNet to analyze tissue microstructure in mouse and human liver tissue. TiMiGNet shows high performance in predicting structures like bile canaliculi, sinusoids, and Kupffer cell shapes from actin meshwork images. Remarkably, using TiMiGNet we were able to computationally reconstruct tissue structures that cannot be directly imaged due experimental limitations in deep dense tissues, a significant advancement in deep tissue imaging. Our open-source virtual prediction tool facilitates accessible and efficient multi-species tissue microstructure analysis, accommodating researchers with varying expertise levels. Overall, our method represents a powerful approach for studying tissue microstructure, with far-reaching applications in diverse biological contexts and species.
@article{Bettancourt8763,
author={Nicolás Bettancourt, Cristian Pérez-Gallardo, Valeria Candia, Pamela Guevara, Yannis Kalaidzidis, Marino Zerial, Fabián Segovia-Miranda, Hernán Morales-Navarrete},
title={Virtual tissue microstructure reconstruction across species using generative deep learning.},
journal ={PloS one},
volume={19},
issue ={7},
pages={null--null},
year=2024
}

Michael E Werner, Dylan D Ray, Coleman Breen, Michael F Staddon, Florian Jug, Shiladitya Banerjee, Amy Shaub Maddox
Mechanical and biochemical feedback combine to generate complex contractile oscillations in cytokinesis.
Curr Biol, Art. No. doi: 10.1016/j.cub.2024.06.037 (2024)
PubMed Source   

The actomyosin cortex is an active material that generates force to drive shape changes via cytoskeletal remodeling. Cytokinesis is the essential cell division event during which a cortical actomyosin ring closes to separate two daughter cells. Our active gel theory predicted that actomyosin systems controlled by a biochemical oscillator and experiencing mechanical strain would exhibit complex spatiotemporal behavior. To test whether active materials in vivo exhibit spatiotemporally complex kinetics, we imaged the C. elegans embryo with unprecedented temporal resolution and discovered that sections of the cytokinetic cortex undergo periodic phases of acceleration and deceleration. Contractile oscillations exhibited a range of periodicities, including those much longer periods than the timescale of RhoA pulses, which was shorter in cytokinesis than in any other biological context. Modifying mechanical feedback in vivo or in silico revealed that the period of contractile oscillation is prolonged as a function of the intensity of mechanical feedback. Fast local ring ingression occurs where speed oscillations have long periods, likely due to increased local stresses and, therefore, mechanical feedback. Fast ingression also occurs where material turnover is high, in vivo and in silico. We propose that downstream of initiation by pulsed RhoA activity, mechanical feedback, including but not limited to material advection, extends the timescale of contractility beyond that of biochemical input and, therefore, makes it robust to fluctuations in activation. Circumferential propagation of contractility likely allows for sustained contractility despite cytoskeletal remodeling necessary to recover from compaction. Thus, like biochemical feedback, mechanical feedback affords active materials responsiveness and robustness.
@article{Werner8764,
author={Michael E Werner, Dylan D Ray, Coleman Breen, Michael F Staddon, Florian Jug, Shiladitya Banerjee, Amy Shaub Maddox},
title={Mechanical and biochemical feedback combine to generate complex contractile oscillations in cytokinesis.},
journal ={Current biology : CB},
volume={},
pages={1--1},
year=2024
}

Cedric Landerer, Maxim Scheremetjew, HongKee Moon, Lena Hersemann, Agnes Toth-Petroczy
deTELpy: Python package for high-throughput detection of amino acid substitutions in mass spectrometry datasets.
Bioinformatics, 40(7) Art. No. btae424 (2024)
Open Access PubMed Source Full Text   

Errors in the processing of genetic information during protein synthesis can lead to phenotypic mutations, such as amino acid substitutions, e.g. by transcription or translation errors. While genetic mutations can be readily identified using DNA sequencing, and mutations due to transcription errors by RNA sequencing, translation errors can only be identified proteome-wide using mass spectrometry.
@article{Landerer8744,
author={Cedric Landerer, Maxim Scheremetjew, HongKee Moon, Lena Hersemann, Agnes Toth-Petroczy},
title={deTELpy: Python package for high-throughput detection of amino acid substitutions in mass spectrometry datasets.},
journal ={Bioinformatics (Oxford, England)},
volume={40},
issue ={7},
pages={null--null},
year=2024
}

Julia Flock✳︎, Yexin Xie✳︎, Regis P. Lemaitre, Karine Lapouge, Kim Remans
The Use of Baculovirus-Mediated Gene Expression in Mammalian Cells for Recombinant Protein Production.
Methods Mol Biol, 2810 29-53 (2024)
PubMed Source   

Baculovirus-mediated gene expression in mammalian cells, BacMam, is a useful alternative to transient transfection for recombinant protein production in various types of mammalian cell lines. We decided to establish BacMam in our lab in order to streamline our workflows for gene expression in insect and mammalian cells, as it is straightforward to parallelize the baculovirus generation for both types of eukaryotic cells. This chapter provides a step-by-step description of the protocols we use for the generation of the recombinant BacMam viruses, the transduction of mammalian cell cultures, and optimization of the protein production conditions through small-scale expression and purification tests.
@article{Flock8745,
author={Julia Flock, Yexin Xie, Regis P. Lemaitre, Karine Lapouge, Kim Remans},
title={The Use of Baculovirus-Mediated Gene Expression in Mammalian Cells for Recombinant Protein Production.},
journal ={Methods in molecular biology (Clifton, N.J.)},
volume={2810},
pages={29--53},
year=2024
}

Teije C Middelkoop#, Jonas Neipel, Caitlin E Cornell, Ronald Naumann, Lokesh G Pimpale, Frank Jülicher#, Stephan W. Grill#
A cytokinetic ring-driven cell rotation achieves Hertwig's rule in early development.
Proc Natl Acad Sci U.S.A., 121(25) Art. No. e2318838121 (2024)
Open Access PubMed Source   

Hertwig's rule states that cells divide along their longest axis, usually driven by forces acting on the mitotic spindle. Here, we show that in contrast to this rule, microtubule-based pulling forces in early Caenorhabditis elegans embryos align the spindle with the short axis of the cell. We combine theory with experiments to reveal that in order to correct this misalignment, inward forces generated by the constricting cytokinetic ring rotate the entire cell until the spindle is aligned with the cell's long axis. Experiments with slightly compressed mouse zygotes indicate that this cytokinetic ring-driven mechanism of ensuring Hertwig's rule is general for cells capable of rotating inside a confining shell, a scenario that applies to early cell divisions of many systems.
@article{Middelkoop8735,
author={Teije C Middelkoop, Jonas Neipel, Caitlin E Cornell, Ronald Naumann, Lokesh G Pimpale, Frank Jülicher, Stephan W. Grill},
title={A cytokinetic ring-driven cell rotation achieves Hertwig's rule in early development.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={121},
issue ={25},
pages={null--null},
year=2024
}

Adriano Bolondi✳︎, Benjamin K Law✳︎, Helene Kretzmer, Seher Ipek Gassaloglu, René Buschow, Christina Riemenschneider, Dian Yang, Maria Walther, Jesse V Veenvliet#, Alexander Meissner#, Zachary D Smith#, Michelle M Chan
Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids.
Dev Cell, 59(12) 1489-1505 (2024)
Open Access PubMed Source   

Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types. We find that NMPs show subtle transcriptional signatures related to their recent differentiation and contribute to downstream lineages through a surprisingly broad distribution of individual fate outcomes. Although decision-making can be heavily influenced by environmental cues to induce morphological phenotypes, axial progenitors intrinsically mature over developmental time to favor the neural lineage. Using these data, we present an experimental and analytical framework for exploring the non-homeostatic dynamics of transient progenitor populations as they shape complex tissues during critical developmental windows.
@article{Bolondi8700,
author={Adriano Bolondi, Benjamin K Law, Helene Kretzmer, Seher Ipek Gassaloglu, René Buschow, Christina Riemenschneider, Dian Yang, Maria Walther, Jesse V Veenvliet, Alexander Meissner, Zachary D Smith, Michelle M Chan},
title={Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids.},
journal ={Developmental cell},
volume={59},
issue ={12},
pages={1489--1505},
year=2024
}

Rasmus K Norrild, Thomas O Mason, Lars Boyens-Thiele, Soumik Ray, Joachim B Mortensen, Anatol Fritsch, Juan M Iglesias-Artola, Louise K Klausen, Emil G P Stender, Henrik Jensen, Alexander K Buell
Taylor Dispersion-Induced Phase Separation for the Efficient Characterisation of Protein Condensate Formation.
Angew Chem Int Ed Engl, 63(25) Art. No. e202404018 (2024)
Open Access PubMed Source   

Biomolecular condensates have emerged as important structures in cellular function and disease, and are thought to form through liquid-liquid phase separation (LLPS). Thorough and efficient in vitro experiments are therefore needed to elucidate the driving forces of protein LLPS and the possibility to modulate it with drugs. Here we present Taylor dispersion-induced phase separation (TDIPS), a method to robustly measure condensation phenomena using a commercially available microfluidic platform. It uses only nanoliters of sample, does not require extrinsic fluorescent labels, and is straightforward to implement. We demonstrate TDIPS by screening the phase behaviour of two proteins that form biomolecular condensates in vivo, PGL-3 and Ddx4. Uniquely accessible to this method, we find an unexpected re-entrant behaviour at very low ionic strength, where LLPS is inhibited for both proteins. TDIPS can also probe the reversibility of assemblies, which was shown for both α-synuclein and for lysozyme, relevant for health and biotechnology, respectively. Finally, we highlight how effective inhibition concentrations and partitioning of LLPS-modifying compounds can be screened highly efficiently.
@article{Norrild8729,
author={Rasmus K Norrild, Thomas O Mason, Lars Boyens-Thiele, Soumik Ray, Joachim B Mortensen, Anatol Fritsch, Juan M Iglesias-Artola, Louise K Klausen, Emil G P Stender, Henrik Jensen, Alexander K Buell},
title={Taylor Dispersion-Induced Phase Separation for the Efficient Characterisation of Protein Condensate Formation.},
journal ={Angewandte Chemie (International ed. in English)},
volume={63},
issue ={25},
pages={null--null},
year=2024
}

Alexandra M Garfinkel✳︎, Efe Ilker✳︎, Hidenobu Miyazawa✳︎, Kathrin Schmeisser✳︎, Jason M Tennessen✳︎
Historic obstacles and emerging opportunities in the field of developmental metabolism - lessons from Heidelberg.
Development, 151(12) Art. No. dev202937 (2024)
PubMed Source   

The field of developmental metabolism is experiencing a technological revolution that is opening entirely new fields of inquiry. Advances in metabolomics, small-molecule sensors, single-cell RNA sequencing and computational modeling present new opportunities for exploring cell-specific and tissue-specific metabolic networks, interorgan metabolic communication, and gene-by-metabolite interactions in time and space. Together, these advances not only present a means by which developmental biologists can tackle questions that have challenged the field for centuries, but also present young scientists with opportunities to define new areas of inquiry. These emerging frontiers of developmental metabolism were at the center of a highly interactive 2023 EMBO workshop 'Developmental metabolism: flows of energy, matter, and information'. Here, we summarize key discussions from this forum, emphasizing modern developmental biology's challenges and opportunities.
@article{Garfinkel8746,
author={Alexandra M Garfinkel, Efe Ilker, Hidenobu Miyazawa, Kathrin Schmeisser, Jason M Tennessen},
title={Historic obstacles and emerging opportunities in the field of developmental metabolism - lessons from Heidelberg.},
journal ={Development (Cambridge, England)},
volume={151},
issue ={12},
pages={1--1},
year=2024
}


✳︎ joint first authors, # joint corresponding authors
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