MPI-CBG Publications

Sort by

Showing 21 to 30 of 2,331 entries

Show entries

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
}

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, Art. No. doi: 10.1093/bioinformatics/btae424 (2024)
Open Access PubMed Source

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={},
pages={1--1},
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
}

Zuzana Gelová^✳︎, Alvaro Ingles-Prieto^✳︎, Tina Bohstedt, Fabian Frommelt, Gamma Chi, Yung-Ning Chang, Julio Garcia, Gernot Wolf, Lucia Azzollini, Sara Tremolada, Andreea Scacioc, Jesper S Hansen, Iciar Serrano, Aida Droce, Jenifer Cuesta Bernal, Nicola A Burgess-Brown, Elisabeth P Carpenter, Katharina L Dürr, Peter Kristensen, Eric R Geertsma, Saša Štefanić, Lia Scarabottolo, Tabea Wiedmer, Vera Puetter, David B Sauer, Giulio Superti-Furga
Protein binder toolbox for studies of solute carrier transporters.
J Mol Biol, Art. No. doi: 10.1016/j.jmb.2024.168665 (2024)
PubMed Source

Transporters of the solute carrier superfamily (SLCs) are responsible for the transmembrane traffic of the majority of chemical substances in cells and tissues and are therefore of fundamental biological importance. As is often the case with membrane proteins that can be heavily glycosylated, a lack of reliable high-affinity binders hinders their functional analysis. Purifying and reconstituting transmembrane proteins in their lipidic environments remains challenging and standard approaches to generate binders for multi-transmembrane proteins, such as SLCs, channels or G protein-coupled receptors (GPCRs) are lacking. While generating protein binders to 27 SLCs, we produced full length protein or cell lines as input material for binder generation by selected binder generation platforms. As a result, we obtained 525 binders for 22 SLCs. We validated the binders with a cell-based validation workflow using immunofluorescent and immunoprecipitation methods to process all obtained binders. Finally, we demonstrated the potential applications of the binders that passed our validation pipeline in structural, biochemical, and biological applications using the exemplary protein SLC12A6, an ion transporter relevant in human disease. With this work, we were able to generate easily renewable and highly specific binders against SLCs, which will greatly facilitate the study of this neglected protein family. We hope that the process will serve as blueprint for the generation of binders against the entire superfamily of SLC transporters.

@article{Gelová8737,
author={Zuzana Gelová, Alvaro Ingles-Prieto, Tina Bohstedt, Fabian Frommelt, Gamma Chi, Yung-Ning Chang, Julio Garcia, Gernot Wolf, Lucia Azzollini, Sara Tremolada, Andreea Scacioc, Jesper S Hansen, Iciar Serrano, Aida Droce, Jenifer Cuesta Bernal, Nicola A Burgess-Brown, Elisabeth P Carpenter, Katharina L Dürr, Peter Kristensen, Eric R Geertsma, Saša Štefanić, Lia Scarabottolo, Tabea Wiedmer, Vera Puetter, David B Sauer, Giulio Superti-Furga},
title={Protein binder toolbox for studies of solute carrier transporters.},
journal ={Journal of molecular biology},
volume={},
pages={null--null},
year=2024
}

Jan Gerwin^✳︎, Julián Torres-Dowdall^✳︎^#, Thomas Brown, Axel Meyer^#
Expansion and Functional Diversification of Long-Wavelength-Sensitive Opsin in Anabantoid Fishes.
J Mol Evol, Art. No. doi: 10.1007/s00239-024-10181-0 (2024)
Open Access PubMed Source

Gene duplication is one of the most important sources of novel genotypic diversity and the subsequent evolution of phenotypic diversity. Determining the evolutionary history and functional changes of duplicated genes is crucial for a comprehensive understanding of adaptive evolution. The evolutionary history of visual opsin genes is very dynamic, with repeated duplication events followed by sub- or neofunctionalization. While duplication of the green-sensitive opsins rh2 is common in teleost fish, fewer cases of multiple duplication events of the red-sensitive opsin lws are known. In this study, we investigate the visual opsin gene repertoire of the anabantoid fishes, focusing on the five lws opsin genes found in the genus Betta. We determine the evolutionary history of the lws opsin gene by taking advantage of whole-genome sequences of nine anabantoid species, including the newly assembled genome of Betta imbellis. Our results show that at least two independent duplications of lws occurred in the Betta lineage. The analysis of amino acid sequences of the lws paralogs of Betta revealed high levels of diversification in four of the seven transmembrane regions of the lws protein. Amino acid substitutions at two key-tuning sites are predicted to lead to differentiation of absorption maxima (λmax) between the paralogs within Betta. Finally, eye transcriptomics of B. splendens at different developmental stages revealed expression shifts between paralogs for all cone opsin classes. The lws genes are expressed according to their relative position in the lws opsin cluster throughout ontogeny. We conclude that temporal collinearity of lws expression might have facilitated subfunctionalization of lws in Betta and teleost opsins in general.

@article{Gerwin8742,
author={Jan Gerwin, Julián Torres-Dowdall, Thomas Brown, Axel Meyer},
title={Expansion and Functional Diversification of Long-Wavelength-Sensitive Opsin in Anabantoid Fishes.},
journal ={Journal of molecular evolution},
volume={},
pages={1--1},
year=2024
}

^✳︎ joint first authors, ^# joint corresponding authors