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Suhrid Ghosh✳︎, Anna Körte✳︎, Giulia Serafini✳︎, Vinca Yadav✳︎, Jonathan Rodenfels
Developmental energetics: Energy expenditure, budgets and metabolism during animal embryogenesis.
Semin Cell Dev Biol, 138 83-93 (2023)
Open Access PubMed Source   

Developing embryos are metabolically active, open systems that constantly exchange matter and energy with their environment. They function out of thermodynamic equilibrium and continuously use metabolic pathways to obtain energy from maternal nutrients, in order to fulfill the energetic requirements of growth and development. While an increasing number of studies highlight the role of metabolism in different developmental contexts, the physicochemical basis of embryogenesis, or how cellular processes use energy and matter to act together and transform a zygote into an adult organism, remains unknown. As we obtain a better understanding of metabolism, and benefit from current technology development, it is a promising time to revisit the energetic cost of development and how energetic principles may govern embryogenesis. Here, we review recent advances in methodology to measure and infer energetic parameters in developing embryos. We highlight a potential common pattern in embryonic energy expenditure and metabolic strategy across animal embryogenesis, and discuss challenges and open questions in developmental energetics.
@article{Ghosh8325,
author={Suhrid Ghosh, Anna Körte, Giulia Serafini, Vinca Yadav, Jonathan Rodenfels},
title={Developmental energetics: Energy expenditure, budgets and metabolism during animal embryogenesis.},
journal ={Seminars in cell & developmental biology},
volume={138},
pages={83--93},
year=2023
}

Belin Selcen Beydag-Tasöz, Siham Yennek, Anne Grapin-Botton
Towards a better understanding of diabetes mellitus using organoid models.
Nat Rev Endocrinol, Art. No. doi: 10.1038/s41574-022-00797-x (2023)
PubMed Source   

Our understanding of diabetes mellitus has benefited from a combination of clinical investigations and work in model organisms and cell lines. Organoid models for a wide range of tissues are emerging as an additional tool enabling the study of diabetes mellitus. The applications for organoid models include studying human pancreatic cell development, pancreatic physiology, the response of target organs to pancreatic hormones and how glucose toxicity can affect tissues such as the blood vessels, retina, kidney and nerves. Organoids can be derived from human tissue cells or pluripotent stem cells and enable the production of human cell assemblies mimicking human organs. Many organ mimics relevant to diabetes mellitus are already available, but only a few relevant studies have been performed. We discuss the models that have been developed for the pancreas, liver, kidney, nerves and vasculature, how they complement other models, and their limitations. In addition, as diabetes mellitus is a multi-organ disease, we highlight how a merger between the organoid and bioengineering fields will provide integrative models.
@article{Beydag-Tasöz8507,
author={Belin Selcen Beydag-Tasöz, Siham Yennek, Anne Grapin-Botton},
title={Towards a better understanding of diabetes mellitus using organoid models.},
journal ={Nature reviews. Endocrinology},
volume={},
pages={1--1},
year=2023
}

Ekaterina Osipova, Rico Barsacchi, Tom Brown, Keren Sadanandan, Andrea H Gaede, Amanda Monte, Julia Jarrells, Claudia Moebius, Martin Pippel, Douglas L Altshuler, Sylke Winkler, Marc Bickle, Maude W Baldwin, Michael Hiller
Loss of a gluconeogenic muscle enzyme contributed to adaptive metabolic traits in hummingbirds.
Science, 379(6628) 185-190 (2023)
PubMed Source   

Hummingbirds possess distinct metabolic adaptations to fuel their energy-demanding hovering flight, but the underlying genomic changes are largely unknown. Here, we generated a chromosome-level genome assembly of the long-tailed hermit and screened for genes that have been specifically inactivated in the ancestral hummingbird lineage. We discovered that FBP2 (fructose-bisphosphatase 2), which encodes a gluconeogenic muscle enzyme, was lost during a time period when hovering flight evolved. We show that FBP2 knockdown in an avian muscle cell line up-regulates glycolysis and enhances mitochondrial respiration, coincident with an increased mitochondria number. Furthermore, genes involved in mitochondrial respiration and organization have up-regulated expression in hummingbird flight muscle. Together, these results suggest that FBP2 loss was likely a key step in the evolution of metabolic muscle adaptations required for true hovering flight.
@article{Osipova8502,
author={Ekaterina Osipova, Rico Barsacchi, Tom Brown, Keren Sadanandan, Andrea H Gaede, Amanda Monte, Julia Jarrells, Claudia Moebius, Martin Pippel, Douglas L Altshuler, Sylke Winkler, Marc Bickle, Maude W Baldwin, Michael Hiller},
title={Loss of a gluconeogenic muscle enzyme contributed to adaptive metabolic traits in hummingbirds.},
journal ={Science (New York, N.Y.)},
volume={379},
issue ={6628},
pages={185--190},
year=2023
}

Patrick Cahan#, Barbara Treutlein#
A conversation with ChatGPT on the role of computational systems biology in stem cell research.
Stem Cell Rep, 18(1) 1-2 (2023)
Open Access PubMed Source  

@article{Cahan8501,
author={Patrick Cahan, Barbara Treutlein},
title={A conversation with ChatGPT on the role of computational systems biology in stem cell research.},
journal ={Stem cell reports},
volume={18},
issue ={1},
pages={1--2},
year=2023
}

Qinghao Yu✳︎, Hannah E Walters✳︎, Maximina H Yun
Induction and Characterization of Cellular Senescence in Salamanders.
Methods Mol Biol, 2562 135-154 (2023)
PubMed Source   

Cellular senescence is a permanent proliferation arrest mechanism induced following the detection of genotoxic stress. Mounting evidence has causally linked the accumulation of senescent cells to a growing number of age-related pathologies in mammals. However, recent data have also highlighted senescent cells as important mediators of tissue remodeling during organismal development, tissue repair, and regeneration. As powerful model organisms for studying such processes, salamanders constitute a system in which to probe the characteristics, physiological functions, and evolutionary facets of cellular senescence. In this chapter, we outline methods for the generation, identification, and characterization of salamander senescent cells in vitro and in vivo.
@article{Yu8463,
author={Qinghao Yu, Hannah E Walters, Maximina H Yun},
title={Induction and Characterization of Cellular Senescence in Salamanders.},
journal ={Methods in molecular biology (Clifton, N.J.)},
volume={2562},
pages={135--154},
year=2023
}

Angela L Caipa Garcia, Jill E Kucab, Halh Al-Serori, Rebekah S S Beck, Franziska Fischer, Matthias Hufnagel, Andrea Hartwig, Andrew Floeder, Silvia Balbo, Hayley E Francies, Mathew J Garnett, Meritxell Huch, Jarno Drost, Matthias Zilbauer, Volker M Arlt, David H Phillips
Metabolic Activation of Benzo[a]pyrene by Human Tissue Organoid Cultures.
Int J Mol Sci, 24(1) Art. No. 606 (2022)
Open Access PubMed Source Full Text   

Organoids are 3D cultures that to some extent reproduce the structure, composition and function of the mammalian tissues from which they derive, thereby creating in vitro systems with more in vivo-like characteristics than 2D monocultures. Here, the ability of human organoids derived from normal gastric, pancreas, liver, colon and kidney tissues to metabolise the environmental carcinogen benzo[a]pyrene (BaP) was investigated. While organoids from the different tissues showed varied cytotoxic responses to BaP, with gastric and colon organoids being the most susceptible, the xenobiotic-metabolising enzyme (XME) genes, CYP1A1 and NQO1, were highly upregulated in all organoid types, with kidney organoids having the highest levels. Furthermore, the presence of two key metabolites, BaP-t-7,8-dihydrodiol and BaP-tetrol-l-1, was detected in all organoid types, confirming their ability to metabolise BaP. BaP bioactivation was confirmed both by the activation of the DNA damage response pathway (induction of p-p53, pCHK2, p21 and γ-H2AX) and by DNA adduct formation. Overall, pancreatic and undifferentiated liver organoids formed the highest levels of DNA adducts. Colon organoids had the lowest responses in DNA adduct and metabolite formation, as well as XME expression. Additionally, high-throughput RT-qPCR explored differences in gene expression between organoid types after BaP treatment. The results demonstrate the potential usefulness of organoids for studying environmental carcinogenesis and genetic toxicology.
@article{Garcia8500,
author={Angela L Caipa Garcia, Jill E Kucab, Halh Al-Serori, Rebekah S S Beck, Franziska Fischer, Matthias Hufnagel, Andrea Hartwig, Andrew Floeder, Silvia Balbo, Hayley E Francies, Mathew J Garnett, Meritxell Huch, Jarno Drost, Matthias Zilbauer, Volker M Arlt, David H Phillips},
title={Metabolic Activation of Benzo[a]pyrene by Human Tissue Organoid Cultures.},
journal ={International journal of molecular sciences},
volume={24},
issue ={1},
pages={null--null},
year=2022
}

Lukas Theo Schmitt, Maciej Paszkowski-Rogacz, Florian Jug, Frank Buchholz
Prediction of designer-recombinases for DNA editing with generative deep learning.
Nat Commun, 13(1) Art. No. 7966 (2022)
Open Access PubMed Source Full Text   

Site-specific tyrosine-type recombinases are effective tools for genome engineering, with the first engineered variants having demonstrated therapeutic potential. So far, adaptation to new DNA target site selectivity of designer-recombinases has been achieved mostly through iterative cycles of directed molecular evolution. While effective, directed molecular evolution methods are laborious and time consuming. Here we present RecGen (Recombinase Generator), an algorithm for the intelligent generation of designer-recombinases. We gather the sequence information of over one million Cre-like recombinase sequences evolved for 89 different target sites with which we train Conditional Variational Autoencoders for recombinase generation. Experimental validation demonstrates that the algorithm can predict recombinase sequences with activity on novel target-sites, indicating that RecGen is useful to accelerate the development of future designer-recombinases.
@article{Schmitt8499,
author={Lukas Theo Schmitt, Maciej Paszkowski-Rogacz, Florian Jug, Frank Buchholz},
title={Prediction of designer-recombinases for DNA editing with generative deep learning.},
journal ={Nature communications},
volume={13},
issue ={1},
pages={null--null},
year=2022
}

Shanshan Xu, Maria E Gierisch, Anna Katharina Schellhaus, Ina Poser, Simon Alberti, Florian A Salomons, Nico P Dantuma
Cytosolic stress granules relieve the ubiquitin-proteasome system in the nuclear compartment.
EMBO J, Art. No. doi: 10.15252/embj.2022111802 (2022)
Open Access PubMed Source   

The role of cytosolic stress granules in the integrated stress response has remained largely enigmatic. Here, we studied the functionality of the ubiquitin-proteasome system (UPS) in cells that were unable to form stress granules. Surprisingly, the inability of cells to form cytosolic stress granules had primarily a negative impact on the functionality of the nuclear UPS. While defective ribosome products (DRiPs) accumulated at stress granules in thermally stressed control cells, they localized to nucleoli in stress granule-deficient cells. The nuclear localization of DRiPs was accompanied by redistribution and enhanced degradation of SUMOylated proteins. Depletion of the SUMO-targeted ubiquitin ligase RNF4, which targets SUMOylated misfolded proteins for proteasomal degradation, largely restored the functionality of the UPS in the nuclear compartment in stress granule-deficient cells. Stress granule-deficient cells showed an increase in the formation of mutant ataxin-1 nuclear inclusions when exposed to thermal stress. Our data reveal that stress granules play an important role in the sequestration of cytosolic misfolded proteins, thereby preventing these proteins from accumulating in the nucleus, where they would otherwise infringe nuclear proteostasis.
@article{Xu8498,
author={Shanshan Xu, Maria E Gierisch, Anna Katharina Schellhaus, Ina Poser, Simon Alberti, Florian A Salomons, Nico P Dantuma},
title={Cytosolic stress granules relieve the ubiquitin-proteasome system in the nuclear compartment.},
journal ={The EMBO journal},
volume={},
pages={1--1},
year=2022
}

Linjie Lu, Tristan Guyomar, Quentin Vagne, Rémi Berthoz, Alejandro Torres-Sánchez, Michèle Lieb, Cécilie Martin-Lemaitre, Kobus van Unen, Alf Honigmann, Olivier Pertz, Guillaume Salbreux, Daniel Riveline
Polarity-driven three-dimensional spontaneous rotation of a cell doublet.
bioRxiv, Art. No. doi: https://doi.org/10.1101/2022.12.21.521355 (2022)
Open Access Source Full Text   

Cell mechanical interactions play a fundamental role in the self-organisation of organisms. How these interactions drive coordinated cell movement in three-dimensions remains unclear. Here we report that cell doublets embedded in a 3D extracellular matrix undergo spontaneous rotations and we investigate the rotation mechanism using live cell imaging, quantitative measurements, mechanical perturbations, and theory. We find that rotation is driven by a polarized distribution of myosin within cell cortices. The mismatched orientation of this polarized distribution breaks the doublet mirror symmetry. In addition, cells adhere at their interface through adherens junctions and with the extracellular matrix through focal contacts near myosin clusters. Using a physical theory describing the doublet as two interacting active surfaces, we find that rotation is driven by myosin-generated gradients of active tension, whose profiles are dictated by interacting cell polarity axes. We show that interface three-dimensional shapes can be understood from the Curie principle: shapes symmetries are related to broken symmetries of myosin distribution in cortices. To test for the rotation mechanism, we suppress myosin clusters using laser ablation and we generate new myosin clusters by optogenetics. Our work clarifies how polarity-oriented active mechanical forces drive collective cell motion in three dimensions.
@article{Lu8495,
author={Linjie Lu, Tristan Guyomar, Quentin Vagne, Rémi Berthoz, Alejandro Torres-Sánchez, Michèle Lieb, Cécilie Martin-Lemaitre, Kobus van Unen, Alf Honigmann, Olivier Pertz, Guillaume Salbreux, Daniel Riveline},
title={Polarity-driven three-dimensional spontaneous rotation of a cell doublet.},
journal ={bioRxiv : the preprint server for biology},
volume={},
pages={1--1},
year=2022
}

William E Arter✳︎, Runzhang Qi✳︎, Nadia A Erkamp✳︎, Georg Krainer✳︎, Kieran Didi, Timothy J Welsh, Julia Acker, Jonathan Nixon-Abell, Seema Qamar, Jordina Guillén-Boixet, Titus Franzmann, David Kuster, Anthony Hyman, Alexander Borodavka, Peter St George-Hyslop, Simon Alberti, Tuomas P J Knowles
Biomolecular condensate phase diagrams with a combinatorial microdroplet platform.
Nat Commun, 13(1) Art. No. 7845 (2022)
Open Access PubMed Source Full Text   

The assembly of biomolecules into condensates is a fundamental process underlying the organisation of the intracellular space and the regulation of many cellular functions. Mapping and characterising phase behaviour of biomolecules is essential to understand the mechanisms of condensate assembly, and to develop therapeutic strategies targeting biomolecular condensate systems. A central concept for characterising phase-separating systems is the phase diagram. Phase diagrams are typically built from numerous individual measurements sampling different parts of the parameter space. However, even when performed in microwell plate format, this process is slow, low throughput and requires significant sample consumption. To address this challenge, we present here a combinatorial droplet microfluidic platform, termed PhaseScan, for rapid and high-resolution acquisition of multidimensional biomolecular phase diagrams. Using this platform, we characterise the phase behaviour of a wide range of systems under a variety of conditions and demonstrate that this approach allows the quantitative characterisation of the effect of small molecules on biomolecular phase transitions.
@article{Arter8491,
author={William E Arter, Runzhang Qi, Nadia A Erkamp, Georg Krainer, Kieran Didi, Timothy J Welsh, Julia Acker, Jonathan Nixon-Abell, Seema Qamar, Jordina Guillén-Boixet, Titus Franzmann, David Kuster, Anthony Hyman, Alexander Borodavka, Peter St George-Hyslop, Simon Alberti, Tuomas P J Knowles},
title={Biomolecular condensate phase diagrams with a combinatorial microdroplet platform.},
journal ={Nature communications},
volume={13},
issue ={1},
pages={null--null},
year=2022
}


✳︎ joint first authors, # joint corresponding authors
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