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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
}

Anja Roden, Melanie K Engelin, Klaas M Pos, Eric R Geertsma
Membrane-anchored substrate binding proteins are deployed in secondary TAXI transporters.
Biol Chem, Art. No. doi: 10.1515/hsz-2022-0337 (2023)
Open Access PubMed Source   

Substrate-binding proteins (SBPs) are part of solute transport systems and serve to increase substrate affinity and uptake rates. In contrast to primary transport systems, the mechanism of SBP-dependent secondary transport is not well understood. Functional studies have thus far focused on Na+-coupled Tripartite ATP-independent periplasmic (TRAP) transporters for sialic acid. Herein, we report the in vitro functional characterization of TAXIPm-PQM from the human pathogen Proteus mirabilis. TAXIPm-PQM belongs to a TRAP-subfamily using a different type of SBP, designated TRAP-associated extracytoplasmic immunogenic (TAXI) protein. TAXIPm-PQM catalyzes proton-dependent α-ketoglutarate symport and its SBP is an essential component of the transport mechanism. Importantly, TAXIPm-PQM represents the first functionally characterized SBP-dependent secondary transporter that does not rely on a soluble SBP, but uses a membrane-anchored SBP instead.
@article{Roden8511,
author={Anja Roden, Melanie K Engelin, Klaas M Pos, Eric R Geertsma},
title={Membrane-anchored substrate binding proteins are deployed in secondary TAXI transporters.},
journal ={Biological chemistry},
volume={},
pages={null--null},
year=2023
}

Mateusz Susik, Ivo F. Sbalzarini
Analysis of the Hamiltonian Monte Carlo genotyping algorithm on PROVEDIt mixtures including a novel precision benchmark.
Forensic Sci Int Genet, 64 Art. No. 102840 (2023)
Open Access   PubMed Source   

We provide an internal validation study of a recently published precise DNA mixture algorithm based on Hamiltonian Monte Carlo sampling (Susik et al., 2022). We provide results for all 428 mixtures analysed by Riman et al. (2021) and compare the results with two state-of-the-art software products: STRmix™  v2.6 and Euroformix v3.4.0. The comparison shows that the Hamiltonian Monte Carlo method provides reliable values of likelihood ratios (LRs) close to the other methods. We further propose a novel large-scale precision benchmark and quantify the precision of the Hamiltonian Monte Carlo method, indicating its improvements over existing solutions. Finally, we analyse the influence of the factors discussed by Buckleton et al. (2022).
@article{Susik8510,
author={Mateusz Susik, Ivo F. Sbalzarini},
title={Analysis of the Hamiltonian Monte Carlo genotyping algorithm on PROVEDIt mixtures including a novel precision benchmark.},
journal ={Forensic science international. Genetics},
volume={64},
pages={null--null},
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
}

Ksenia Kuznetsova, Noémie M Chabot, Martino Ugolini, Edlyn Wu, Manan Lalit, Haruka Oda, Yuko Sato, Hiroshi Kimura, Florian Jug, Nadine Vastenhouw
Nanog organizes transcription bodies.
Curr Biol, 33(1) 164-173 (2023)
PubMed Source Full Text   

The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells.1-3 How proteins of the transcriptional machinery come together to form such bodies, however, is unclear. Here, we take advantage of two large, isolated, and long-lived transcription bodies that reproducibly form during early zebrafish embryogenesis to characterize the dynamics of transcription body formation. Once formed, these transcription bodies are enriched for initiating and elongating RNA polymerase II, as well as the transcription factors Nanog and Sox19b. Analyzing the events leading up to transcription, we find that Nanog and Sox19b cluster prior to transcription. The clustering of transcription factors is sequential; Nanog clusters first, and this is required for the clustering of Sox19b and the initiation of transcription. Mutant analysis revealed that both the DNA-binding domain as well as one of the two intrinsically disordered regions of Nanog are required to organize the two bodies of transcriptional activity. Taken together, our data suggest that the clustering of transcription factors dictates the formation of transcription bodies.
@article{Kuznetsova8487,
author={Ksenia Kuznetsova, Noémie M Chabot, Martino Ugolini, Edlyn Wu, Manan Lalit, Haruka Oda, Yuko Sato, Hiroshi Kimura, Florian Jug, Nadine Vastenhouw},
title={Nanog organizes transcription bodies.},
journal ={Current biology : CB},
volume={33},
issue ={1},
pages={164--173},
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
}
✳︎ joint first authors, # joint corresponding authors
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