Systems biology

  • Article
    | Open Access

    Macrophage is located in different tissue to serve diverse functions. Here the authors use mass spectrometry and bulk RNA-sequencing to profile 11 mouse macrophage populations from 8 tissues, and combine their de novo data with public datasets to report an integrated proteomic and transcriptomic landscape of mouse macrophage as a valuable resource.

    • Jingbo Qie
    • , Yang Liu
    •  & Chen Ding
  • Article
    | Open Access

    Here, the authors present a method to build genetically personalised metabolic models across tissues to estimate individualised reaction fluxes. A fluxome-wide association study in UK Biobank identifies fluxes associated with metabolites and coronary artery disease.

    • Carles Foguet
    • , Yu Xu
    •  & Michael Inouye
  • Article
    | Open Access

    Artificial receptors targeted to the secretory pathway often fail to exhibit the expected activity due to post-translational modifications and/or improper folding. Here, the authors engineer diverse synthetic receptors that reside in the cytoplasm, inside the endoplasmic reticulum, or on the plasma membrane through orientation adjustment of the receptor parts and by elimination of dysfunctional PTMs sites.

    • Mohamed Mahameed
    • , Pengli Wang
    •  & Martin Fussenegger
  • Article
    | Open Access

    Protein phosphorylation is a ubiquitous post-translational modification used to regulate cellular processes and proteome architecture by modulating protein-protein interactions. Here the authors optimize genetically encoded phosphothreonine to study the regulation of CHK2 kinase using large-scale DNA arrays that enable phosphoproteome expression techniques to identify sitespecific overlap between CHK2 substrates and 14-3-3 interactions.

    • Jack M. Moen
    • , Kyle Mohler
    •  & Jesse Rinehart
  • Article
    | Open Access

    The UCLA Ribonomics group reports that the nuclear export efficiency of innate immune mRNAs varies over a hundred-fold range such that for many genes only a small fraction of the newly synthesized premRNA reaches the cytoplasm. They show that nuclear export and cytoplasmic decay rates are correlated thereby ensuring similar expression levels of short-lived and long-lived mRNAs.

    • Diane Lefaudeux
    • , Supriya Sen
    •  & Sri Kosuri
  • Article
    | Open Access

    Environmental exposures in early life can have lasting health effects, but the molecular mechanisms are not well understood. Here, the authors discover >1000 associations between exposure factors and child multi-omics profiles, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions.

    • Léa Maitre
    • , Mariona Bustamante
    •  & Martine Vrijheid
  • Article
    | Open Access

    By comprehensively mapping the impact that different classes of mutations (substitutions, insertions, deletions) have on the ability of the amyloid beta peptide to nucleate amyloids, the authors identify a large set of likely pathogenic variants of amyloid beta that are specifically enriched at its polar N-terminal region.

    • Mireia Seuma
    • , Ben Lehner
    •  & Benedetta Bolognesi
  • Article
    | Open Access

    Heterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here the authors present a tunable, modular, and portable feedforward controller that allows dynamic modulation of a genes expression to possibly high-levels without substantially affecting growth rate.

    • Carlos Barajas
    • , Hsin-Ho Huang
    •  & Domitilla Del Vecchio
  • Article
    | Open Access

    Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.

    • Jie Sun
    • , Ming Wang
    •  & Baohua Liu
  • Article
    | Open Access

    Ant and honeybee workers specialize on certain tasks and also on zones within the nest; but how do they avoid straying into the wrong zone? The authors conduct automated tracking experiments following thousands of individuals, revealing that workers use context-dependent rules to navigate inside the nest.

    • Thomas O. Richardson
    • , Nathalie Stroeymeyt
    •  & Laurent Keller
  • Article
    | Open Access

    Modification of transcribed mRNAs enables regulation of transcription but its extent in cancer cells is incompletely understood. Here, the authors analyse transcript assembly in over 1000 cancer cell lines and find unannotated transcripts are common, and are associated with drug sensitivity.

    • Wei Hu
    • , Yangjun Wu
    •  & Shengli Li
  • Article
    | Open Access

    The ability to externally control gene expression has been important for all areas of biological research, especially for synthetic biology. Here the authors present plasmid TULIP which offers DNA copy number control via chemical induction to accelerate the design, prototyping, and reuse of gene circuits in diverse contexts.

    • Shivang Hina-Nilesh Joshi
    • , Chentao Yong
    •  & Andras Gyorgy
  • Article
    | Open Access

    A challenge in synthetic biology is the empirical characterisation of genetic parts. Here the authors present FPCountR, a validated method and accompanying R package that enables the precise quantification of fluorescent protein reporters per bacterial cell to be enumerated in ‘proteins per cell’ or nanomolar units without requiring protein purification.

    • Eszter Csibra
    •  & Guy-Bart Stan
  • Article
    | Open Access

    Renal fibrosis is a progressive process with complex etiopathology, causing organ failure. Here authors present a mathematical model, based on an in vitro system faithfully contemplating macrophage-fibroblast interaction and the metabolic-immunologic signals that are affecting kidney fibrosis, that is applicable to kidney transplant failure.

    • Elisa Setten
    • , Alessandra Castagna
    •  & Massimo Locati
  • Article
    | Open Access

    β-TrCP plays an important role in diverse cellular processes such as the cell cycle and inflammation. Here the authors develop a biosensor for β-TrCP activity and use it to investigate β-TrCP dynamics during the cell cycle, and to screen a small-molecule library for β-TrCP activators and inhibitors.

    • Debasish Paul
    • , Stephen C. Kales
    •  & Steven D. Cappell
  • Article
    | Open Access

    The sensory cortices of many mammals consist of modules in the form of cortical columns. By analyzing functional connectivity and neural responses to visual stimuli, the authors show that this organization may extend to the human temporal lobe.

    • Julio I. Chapeton
    • , John H. Wittig Jr
    •  & Kareem A. Zaghloul
  • Article
    | Open Access

    Protein abundance is controlled at the transcriptional, translational and posttranslational levels. Here, Öztürk et al. determine proteome changes resulting from individual knockout of 3308 nonessential genes in the yeast S. pombe, infer gene functionality, and show that protein upregulation under stable transcript expression utilizes optimal codons.

    • Merve Öztürk
    • , Anja Freiwald
    •  & Falk Butter
  • Article
    | Open Access

    Constructing a minimal protein machinery for self-division of membrane compartments is a major goal of bottom-up synthetic biology. Here, authors achieved the assembly, placement and onset of contraction of a minimal division ring in lipid vesicles.

    • Shunshi Kohyama
    • , Adrián Merino-Salomón
    •  & Petra Schwille
  • Article
    | Open Access

    Here the authors address how embryos control the timing of specific gene activation in early frog development. They find transcription factors for early gene activation are maternally loaded and remain at constant levels, and rather that order of activation is based on their sequential entry into the nucleus based largely on their respective affinity to importins.

    • Thao Nguyen
    • , Eli J. Costa
    •  & Martin Wühr
  • Article
    | Open Access

    HOXA9 plays an important role in acute myeloid leukaemia (AML), but its relevance for other blood malignancies is unclear. Here, the authors show that HOXA9 has a binary switch function that can clinically stratify AML patients, and model how the interactions with JAK2, TET2 and NOTCH impact myeloproliferative neoplasms.

    • Laure Talarmain
    • , Matthew A. Clarke
    •  & Benjamin A. Hall
  • Article
    | Open Access

    Pesticide impact on honey bees under field conditions remains elusive. Here, the authors combine a systems biology approach and laboratory experiments to show that the immune suppressive effect of the pathogen deformed wing virus can be responsible for the disparity amongst honey bee experiments.

    • Dimitri Breda
    • , Davide Frizzera
    •  & Francesco Nazzi
  • Article
    | Open Access

    Computational properties of neuronal networks have been applied to computing systems using simplified models comprising repeated connected nodes. Here the authors create layered assemblies of genetically encoded devices that perform non-binary logic computation and signal processing using combinatorial promoters and feedback regulation.

    • Luna Rizik
    • , Loai Danial
    •  & Ramez Daniel
  • Article
    | Open Access

    Here, Diot et al. use the nematode Caenorhabditis elegans as a model to identify off-target toxicity mechanisms for tamoxifen, and find that these include fatty acid metabolism and cell death, which can be modulated by different bacterial species.

    • Cédric Diot
    • , Aurian P. García-González
    •  & Albertha J. M. Walhout
  • Article
    | Open Access

    Engineered living materials (ELMs) embed living cells in a biopolymer matrix to create novel materials with tailored functions. In this work, the authors engineered bacteria to grow novel macroscopic materials that can be reshaped, functionalized, and used to filter contaminated water while also showing that the stiffness of these materials can be tuned through genetic changes.

    • Sara Molinari
    • , Robert F. Tesoriero Jr.
    •  & Caroline M. Ajo-Franklin
  • Article
    | Open Access

    Biosynthetic pathway of dencichine, a plant derived nature product that has found various pharmacological applications, is still elusive. Here, the authors design artificial pathways through retro-biosynthesis approaches and achieve its efficient production in E. coli by systematic metabolic and enzymatic engineering.

    • Wenna Li
    • , Zhao Zhou
    •  & Qipeng Yuan
  • Article
    | Open Access

    Protein networks have been widely explored but most binding affinities remain unknown, limiting the quantitative interpretation of interactomes. Here the authors measure affinities of 65,000 interactions involving human PDZ domains and target sequence motifs relevant for viral infection and cancer.

    • Gergo Gogl
    • , Boglarka Zambo
    •  & Gilles Travé
  • Article
    | Open Access

    There are competing hypotheses for human herpes simplex virus 2’s migration out-of-Africa. Here, the authors sequence 65 new herpes simplex virus 2 genomes with a focus on under-sampled sub-Saharan African countries, suggesting an Eastern African origin for global dispersal the virus between 22-29 thousand years ago.

    • Jennifer L. Havens
    • , Sébastien Calvignac-Spencer
    •  & Joel O. Wertheim
  • Article
    | Open Access

    Layered feedback is an optimization strategy in feedback control designs widely used in engineering. Here, combining simulation and experimentation, the authors apply layered control - a powerful optimization strategy in engineering - to synthetic biomolecular networks in living bacteria to show layered control overcomes performance trade-offs in biology.

    • Chelsea Y. Hu
    •  & Richard M. Murray
  • Article
    | Open Access

    Unlike eukaryotic system, bacterial hosts lack membranous system, which is one of the limitations for efficient metabolic engineering. Here, the authors report a kinetic compartmentalization strategy to increase substrate availability from competitive reactions for the efficient production of itaconate in E. coli.

    • Dae-yeol Ye
    • , Myung Hyun Noh
    •  & Gyoo Yeol Jung
  • Article
    | Open Access

    Arising through multiple binding elements, multivalency can specify the avidity, duration, cooperativity, and selectivity of biomolecular interactions, but quantitative prediction and design of these properties has remained challenging. Here the authors enable facile analysis and engineering of multivalent binding by developing MVsim, a simulator that incorporates biochemical and biophysical parameters of interacting molecules and is accessible through a graphical user interface.

    • Bence Bruncsics
    • , Wesley J. Errington
    •  & Casim A. Sarkar
  • Article
    | Open Access

    Transcription rates are regulated by the interactions between RNA polymerase, sigma factor, and promoter DNA sequences in bacteria. Here the authors combine massively parallel experiments & machine learning to develop a predictive biophysical model of transcription, validated across 22132 bacterial promoters, and apply it to the design and debugging of genetic circuits.

    • Travis L. LaFleur
    • , Ayaan Hossain
    •  & Howard M. Salis
  • Article
    | Open Access

    Design of de novo synthetic regulatory DNA is a promising avenue to control gene expression in biotechnology and medicine. Here the authors present EspressionGAN, a generative adversarial network that uses genomic and transcriptomic data to generate regulatory sequences.

    • Jan Zrimec
    • , Xiaozhi Fu
    •  & Aleksej Zelezniak
  • Article
    | Open Access

    Automated design and build processes can rapidly accelerate work in synthetic biology and metabolic engineering. Here the authors present Galaxy-SynBioCAD, a toolshed for synthetic biology, metabolic engineering, and industrial biotechnology that they use to build and execute Galaxy scientific workflows from pathway design to strain engineering through the automated generation of scripts driving robotic workstations.

    • Joan Hérisson
    • , Thomas Duigou
    •  & Jean-Loup Faulon
  • Article
    | Open Access

    The mammalian circadian clock is composed of clock genes forming transcriptional feedback loops. Here, the authors identify a key role of the secondary feedback loop that is interlocked with the core loop to establish a perturbation-resilient clock system.

    • Yasuko O. Abe
    • , Hikari Yoshitane
    •  & Yoshitaka Fukada
  • Article
    | Open Access

    Toe-hold-mediated strand displacement (DSD) is a widely used molecular tool in applications such as DNA computing and nucleic acid diagnostics. Here the authors characterize dozens of orthogonal barcode sequences that can be used for monitoring the output kinetics of multiplexed DSD reactions in real-time using a commercially-available portable nanopore array device.

    • Karen Zhang
    • , Yuan-Jyue Chen
    •  & Jeff Nivala
  • Article
    | Open Access

    This mathematical modelling study projects the dynamics of SARS-CoV-2 in England until the end of 2022 assuming that the Omicron BA.2 sublineage remains dominant. They show that booster vaccination was highly effective in mitigating severe outcomes and that future dynamics will depend greatly on assumptions about waning immunity.

    • Rosanna C. Barnard
    • , Nicholas G. Davies
    •  & W. John Edmunds
  • Article
    | Open Access

    Sun et al. has studied the genetically encodable halotyrosines in proteins of the prokaryotic cell division machinery to elucidate the general role of halogenation in cellular lifespan and oxidative damage-induced diseases such as aging and cancer.

    • Huan Sun
    • , Haiyang Jia
    •  & Nediljko Budisa
  • Article
    | Open Access

    Communities of microbes play important roles in natural environments and hold great potential for deploying division-of-labor strategies in synthetic biology and bioproduction. Here, in a community of two competing E. coli strains, the authors show that the relative abundances of the strains can be stabilized and steered dynamically with remarkable precision by coupling the cells to an automated computer-controlled feedback-loop.

    • Joaquín Gutiérrez Mena
    • , Sant Kumar
    •  & Mustafa Khammash
  • Article
    | Open Access

    Understanding the function of GPCRs requires stimulation with their specific ligands. Here, the authors design chemogenetic G-protein coupled receptors that allows for the study of receptors without knowing the immediate ligand, and demonstrate its use for the β2-adrenergic receptor in microglia.

    • Rouven Schulz
    • , Medina Korkut-Demirbaş
    •  & Sandra Siegert