Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Within microbial communities, microorganisms adopt different lifestyle strategies to use the available resources. Here, the authors use an integrated ‘multi-omic’ approach to study niche breadth (generalist versus specialist lifestyles) in oleaginous microbial assemblages from an anoxic wastewater treatment tank.

    • Emilie E. L. Muller
    • , Nicolás Pinel
    •  & Paul Wilmes

  • Article |

    The use of alternative polyadenylation sites can potentially result in mRNA being more or less susceptible to interaction with modulators of translation or stability. Here Gruber et al. find that the shortening of 3′UTRs observed in proliferating T cells does not significantly impact protein abundance.

    • Andreas R. Gruber
    • , Georges Martin
    •  & Mihaela Zavolan

  • Article |

    Whether the specificity of a TCR can be changed in vitroto recognize an entirely different peptide has not been shown. Here, the authors use directed evolution to change the specificity of a human TCR from recognition of a viral peptide to that of a melanoma antigen.

    • Sheena N. Smith
    • , Yuhang Wang
    •  & David M. Kranz

  • Article |

    Engineering gene expression systems that can be programmed to respond to specific environmental conditions is challenging. Here, the authors develop a synthetic bow-tie circuit that is able to sense signals from microRNA molecules and affect a change in protein dynamics in mammalian cells.

    • Laura Prochazka
    • , Bartolomeo Angelici
    •  & Yaakov Benenson

  • Article
    | Open Access

    Constructing gene circuits with predefined behaviours is typically done on a case-by-case basis. Schaerli et al.instead computationally explore the design space for 3-node networks that generate a stripe in response to a morphogen gradient, and build networks based on their simplest possible forms.

    • Yolanda Schaerli
    • , Andreea Munteanu
    •  & Mark Isalan

  • Article
    | Open Access

    The transcription factor E2F is critical for determining cell proliferation. By monitoring E2F activity in single cells throughout the cell cycle, Dong et al.provide evidence that Myc and G1 cyclin/CDKs regulate different aspects of E2F temporal dynamics, resulting in distinct phenotypic outputs.

    • Peng Dong
    • , Manoj V. Maddali
    •  & Lingchong You

  • Article |

    The quantitative relationship between the fluctuation of specific extrinsic and intrinsic factors, and stochastic fluctuations in gene expression - or noise - has not been clearly established. Here, Yang et al.demonstrate that intrinsic noise is independent of - while extrinsic noise scales linearly with - variation in RNA polymerase abundance.

    • Sora Yang
    • , Seunghyeon Kim
    •  & Nam Ki Lee

  • Article
    | Open Access

    Infection remains a leading cause of morbidity and mortality in neonates worldwide. Here the authors report disproportionate immune stimulatory, co-inhibitory and metabolic pathway responses that specifically mark bacterial infection and can be used to predict sepsis in neonatal patients at the first clinical signs of infection.

    • Claire L. Smith
    • , Paul Dickinson
    •  & Peter Ghazal

  • Article
    | Open Access

    The ability to control antibody binding could have important medical implications. Here, the authors present a method to engineer phosphatase-controllable antibodies that bind to a specific recognition site in the presence of two biomarker inputs.

    • Smita B. Gunnoo
    • , Helene M. Finney
    •  & Benjamin G. Davis

  • Article
    | Open Access

    Neural circuits are functional ensembles of neurons that are selectively interconnected by chemical or electrical synapses. Here the authors describe an approach to the study of neural circuits in C. eleganswhereby electrical synapses are introduced between previously unconnected neurons to reprogram behaviour.

    • Ithai Rabinowitch
    • , Marios Chatzigeorgiou
    •  & William R. Schafer

  • Article |

    In vitro biochemical pathways could provide the high yields required for economical commodity chemical production, but require circuitry development to regulate high-energy cofactors. Here, the authors design and test a simple purge valve system to maintain NADP+/NADPH balance in E. coli.

    • Paul H. Opgenorth
    • , Tyler P. Korman
    •  & James U. Bowie

  • Article
    | Open Access

    Hes1 is an important regulator of progenitor maintenance and timed differentiation, which shows oscillatory expression. Here, the authors combine experimental data and mathematical modelling to show that the interaction between miRNA-9 and Hes1 can predict progenitor transition from one cell state to another, as well as the timing of this transition.

    • Marc Goodfellow
    • , Nicholas E. Phillips
    •  & Nancy Papalopulu

  • Article
    | Open Access

    Actin-dependent motility is driven by the rapid changes in the recruitment of many different structural and regulatory proteins at the cell’s cortex. Sobczyk et al. characterize these changes in the cytoskeletal proteome on a second to minute timescale during chemotactic response in Dictyosteliumusing SILAC-based proteomics.

    • Grzegorz J. Sobczyk
    • , Jun Wang
    •  & Cornelis J. Weijer

  • Article |

    Incomplete oxidation of fuels is a common problem in enzymatic fuel cells and it leads to low energy densities. Zhu et al. report the complete oxidation of sugar in an enzymatic fuel cell through a synthetic enzymatic pathway, which exhibits higher energy densities than lithium-ion batteries.

    • Zhiguang Zhu
    • , Tsz Kin Tam
    •  & Y. -H. Percival Zhang

  • Article |

    Synthetic gene circuits can be programmed in living cells to perform diverse cellular functions. Here, the authors program a genetic circuit that performs a Pavlovian-like learning and recall function in E. coli, and demonstrate the dynamic nature of this conditioning process at a population level.

    • Haoqian Zhang
    • , Min Lin
    •  & Qi Ouyang

  • Article |

    Alterations in hepatocyte metabolism can lead to disorders such as non-alcoholic steatohepatitis (NASH). Here the authors create a comprehensive model of hepatocyte metabolism and use it to identify metabolic pathways altered in disease, revealing that serine levels are reduced in patients with NASH.

    • Adil Mardinoglu
    • , Rasmus Agren
    •  & Jens Nielsen

  • Article |

    Identifying functionally important features of complex biological networks is computationally challenging. Ganter et al.develop a probabilistic framework that uses recurrent metabolite patterns to predict the properties and existence of reactions within a genome-scale metabolic network.

    • Mathias Ganter
    • , Hans-Michael Kaltenbach
    •  & Jörg Stelling

  • Article |

    Microbial community function depends on metabolic interdependencies between individual species, some of which include electron transfer. Nagarajan et al. use genomic, transcriptomic and modelling approaches to describe the mechanisms supporting the syntrophic relationship between Geobacter metallireducens and Geobacter sulfurreducens.

    • Harish Nagarajan
    • , Mallory Embree
    •  & Karsten Zengler

  • Article
    | Open Access

    The effect of the rate of forming and breaking social ties on cooperative behaviour is not clear. Here the authors experimentally test the effect of rewiring the connections between individuals, and find that optimal levels of cooperation are achieved at intermediate levels of change in ties.

    • Hirokazu Shirado
    • , Feng Fu
    •  & Nicholas A. Christakis

  • Article |

    MicroRNAs are thought to confer robustness to biological processes, but clear experimental evidence is still needed. Here, Siciliano et al. construct a toggle-switch in mammalian cells to show that microRNAs buffer fluctuations in protein levels, thereby providing phenotypic robustness to gene regulatory networks.

    • Velia Siciliano
    • , Immacolata Garzilli
    •  & Diego di Bernardo

  • Article
    | Open Access

    Artificial genetic circuits have been designed to enable precise control of cellular behaviour and phenotypes. Saito and colleagues present a new RNA module that can invert the function of a translational OFF to an ON switch and demonstrate its utility in mammalian cells.

    • Kei Endo
    • , Karin Hayashi
    •  & Hirohide Saito

  • Article |

    The ability to induce metabolic pathways in response to a changing environment is an important component of bacterial fitness. Bartl et al. identify optimal programmes for metabolic pathway activation depending on protein synthesis capacity constraints, and demonstrate their impact on operonic organization.

    • Martin Bartl
    • , Martin Kötzing
    •  & Christoph Kaleta

  • Article |

    The complexity and dynamic range of mammalian proteomes has stymied comprehensive protein quantification for the past twenty years. Zhou et al. develop DEEP SEQ mass spectrometry and use it to quantify a murine stem cell proteome to a depth equivalent to RNA-seq-based ribosome profiling.

    • Feng Zhou
    • , Yu Lu
    •  & Jarrod A. Marto

  • Article |

    Nonlinearity is a hallmark of complex networks, but has generally been regarded as an obstacle to controlling their behaviour. Here Cornelius et al.show how nonlinear dynamics can be harnessed to control a network and drive it to desired states.

    • Sean P. Cornelius
    • , William L. Kath
    •  & Adilson E. Motter

  • Article |

    Live cell imaging have recently revealed that transcription factors spend up to 4 min to find and bind their chromosomal binding site. Grönlund et al. show that this slow search process leads to tradeoffs between strength and speed of negative autoregulation for effective noise suppression.

    • Andreas Grönlund
    • , Per Lötstedt
    •  & Johan Elf

  • Article |

    Natural populations are complex systems where interactions can lead to chaotic dynamics. This study tests how cyclic and chaotic microbial predator–prey communities synchronize, showing different phase-locking responses for cyclic and chaotic systems.

    • Lutz Becks
    •  & Hartmut Arndt

  • Article |

    How the sensitivity of biological and pharmacological signalling responses is controlled is poorly understood. Here, computational analyses and cellular experiments show that the sensitivity of a simple biochemical reaction to activators and inhibitors is controlled by negative regulation of cellular signalling.

    • Yu Toyoshima
    • , Hiroaki Kakuda
    •  & Shinya Kuroda

  • Article |

    Humans are a network of complex physiological systems, but quantifying these diverse systems is a challenge. This study presents a method to show that each physiological state is characterized by a specific network structure, demonstrating a connection between network topology and function.

    • Amir Bashan
    • , Ronny P. Bartsch
    •  & Plamen Ch. Ivanov

  • Article
    | Open Access

    GALgenes enhance their own transcription via the transcription factor Gal4p, and the number of Galp4 sites in a promoter is expected to strengthen the feedback. In this study, Hsuet al. show that instead the feedback loops are activated by genes that have frequent bursts of expression and fast RNA decay kinetics.

    • Chieh Hsu
    • , Simone Scherrer
    •  & Attila Becskei

  • Article
    | Open Access

    Experience-dependent plasticity and functional adaptation are thought to be restricted to the central nervous and immune systems. This study shows that long-lasting experience-dependent plasticity is a key feature of endocrine cell networks, allowing improved tissue function and hormone output following repeat demand.

    • David J. Hodson
    • , Marie Schaeffer
    •  & Patrice Mollard

  • Article |

    Direct negative feedback decreases fluctuations in homoeostatic control, but intracellular regulatory systems are indirect. Here, an analytical expression is derived to show that indirect feedback in transcription and translation leads to more fluctuations for intermediate delays but not for long delays.

    • Andreas Grönlund
    • , Per Lötstedt
    •  & Johan Elf

  • Article
    | Open Access

    Sixty years ago it was suggested that the sickle cell disease mutation survives because the heterozygous genotype confers resistance to malaria, resulting in correlation of the two geographical distributions. The authors use a new global assembly of sickle allele frequencies to support this hypothesis at the global scale.

    • Frédéric B. Piel
    • , Anand P. Patil
    •  & Simon I. Hay

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