Systems biology articles within Nature Communications

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  • 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

  • Article
    | Open Access

    The invention of the Fourier integral in the 19th century laid the foundation for modern spectral analysis methods. Here the authors develop frequency-based methods for analyzing the reaction mechanisms within living cells from distinctively noisy single-cell output trajectories and present forward engineering of synthetic oscillators and controllers.

    • Ankit Gupta
    •  & Mustafa Khammash

  • Article
    | Open Access

    Site-specific recombination (SSR) is an important tool in synthetic biology, but its applications are limited by the inability to predictably tune SSR reaction rates. Here, using quantitative high-throughput experiments and machine learning, the authors achieve rational control of a DNA attachment site sequence to predictably modulate site-specific recombination rates both in vitro and in cells.

    • Qiuge Zhang
    • , Samira M. Azarin
    •  & Casim A. Sarkar

  • Article
    | Open Access

    The bacterium E. coli has around 300 transcriptional factors, but the functions of many of them, and the interactions between their respective regulatory networks, are unclear. Here, the authors study genetic interactions among all transcription factor genes in E. coli, revealing condition-dependent interactions and roles for uncharacterized transcription factors.

    • Alla Gagarinova
    • , Ali Hosseinnia
    •  & Mohan Babu

  • Article
    | Open Access

    A critical task in spatial transcriptomics analysis is to understand inherently spatial relationships among cells. Here, the authors present a deep learning framework to integrate spatial and transcriptional information, spatially extending pseudotime and revealing spatiotemporal organization of cells.

    • Honglei Ren
    • , Benjamin L. Walker
    •  & Qing Nie

  • Article
    | Open Access

    Thorough evaluation of CRISPR RNA-guided nucleases off-targets in cells is required for advancing gene therapies. Here the authors report SURRO-seq for the simultaneous investigation of thousands of off-target sites for therapeutic RNA-guided nucleases in cells.

    • Xiaoguang Pan
    • , Kunli Qu
    •  & Yonglun Luo

  • Article
    | Open Access

    The dia-PASEF technology uses ion mobility separation to reduce signal interferences and increase sensitivity of mass spectrometry-based proteomics. The authors present algorithms and a software solution, which boost proteomic depth in dia-PASEF experiments by up to 83% compared to previous work, and are specifically beneficial for fast proteomic experiments and those with low sample amounts.

    • Vadim Demichev
    • , Lukasz Szyrwiel
    •  & Markus Ralser

  • Article
    | Open Access

    Whole-cell screening for Mycobacterium tuberculosis inhibitors is complicated by the pathogen’s slow growth and biocontainment requirements. Here the authors develop engineered E. coli as a synthetic biology tool to express and screen metabolic targets from Mycobacterium tuberculosis.

    • Nadine Bongaerts
    • , Zainab Edoo
    •  & Edwin H. Wintermute

  • Article
    | Open Access

    The range of available copy numbers for cloning vectors is largely restricted to the handful of ORIs that have been isolated from plasmids found in nature. Here the authors introduce a plasmid system that allow for the continuous, finely-tuned control of plasmid copy number between 1 and 800 copies per cell.

    • Miles V. Rouches
    • , Yasu Xu
    •  & Guillaume Lambert

  • Article
    | Open Access

    Our understanding of how compartmentalisation and intercellular communication can tune enzyme reactions is still in its infancy. Here, the authors show that multi-enzyme reactions within semi-permeable compartments have distinct properties compared to reactions in buffer solution.

    • Adrian Zambrano
    • , Giorgio Fracasso
    •  & T-Y. Dora Tang

  • Article
    | Open Access

    Optimization of biological networks is often limited by wet lab labor and cost, and the lack of convenient computational tools. Here, aimed at democratization and standardization, the authors describe METIS, a modular and versatile active machine learning workflow with a simple online interface for the optimization of biological target functions with minimal experimental datasets.

    • Amir Pandi
    • , Christoph Diehl
    •  & Tobias J. Erb

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