Systems biology

  • Letter |

    A computational analysis of the ability of a metabolic reaction network to synthesize all biomass from a single source of carbon and energy shows that when such networks are required to be viable on one particular carbon source, they are typically also viable on multiple other carbon sources that were not targets of selection.

    • Aditya Barve
    •  & Andreas Wagner
  • Article |

    Mycobacterium tuberculosis has the ability to survive within the host for months to decades in an asymptomatic state, and adaptations to hypoxia are thought to have an important role in pathogenesis; here a systems-wide reconstruction of the regulatory network provides a framework for understanding mycobacterial persistence in the host.

    • James E. Galagan
    • , Kyle Minch
    •  & Gary K. Schoolnik
  • Letter |

    Single-cell RNA sequencing is used to investigate the transcriptional response of 18 mouse bone-marrow-derived dendritic cells after lipopolysaccharide stimulation; many highly expressed genes, such as key immune genes and cytokines, show bimodal variation in both transcript abundance and splicing patterns. This variation reflects differences in both cell state and usage of an interferon-driven pathway involving Stat2 and Irf7.

    • Alex K. Shalek
    • , Rahul Satija
    •  & Aviv Regev
  • Letter |

    Saccharomyces cerevisiae is engineered to produce high concentrations of artemisinic acid, a precursor of the artemisinin used in combination therapies for malaria treatment; an efficient and practical chemical process to convert artemisinic acid to artemisinin is also developed.

    • C. J. Paddon
    • , P. J. Westfall
    •  & J. D. Newman
  • Article |

    A global view of the genetic networks regulating the differentiation of TH17 cells is presented, based on temporal expression profiling, computational network reconstruction and validation of predicted interactions by nanowire-mediated siRNA perturbation.

    • Nir Yosef
    • , Alex K. Shalek
    •  & Aviv Regev
  • Letter |

    A mathematical method, known as ergodic rate analysis, has been developed and used to study the rates of molecular events from single time measurements of large populations of fixed cells; this new method is able to overcome some of the previous limitations with regards to studying cell-size control.

    • Ran Kafri
    • , Jason Levy
    •  & Marc W. Kirschner
  • Letter |

    A high-throughput mutagenesis study in a PDZ domain shows that biochemical function and adaptation primarily originate from a collectively evolving amino acid network within the structure termed a protein sector.

    • Richard N. McLaughlin Jr
    • , Frank J. Poelwijk
    •  & Rama Ranganathan
  • Letter |

    Although zebrafish is an important animal model for basic vertebrate biology and human disease modelling, rapid targeted genome modification has not been possible in this species; here a technique based on improved artificial transcription activator-like effector nucleases (TALENs) allows precise sequence modifications at pre-determined genomic locations.

    • Victoria M. Bedell
    • , Ying Wang
    •  & Stephen C. Ekker
  • Article
    | Open Access

    A description is given of the ENCODE consortium’s efforts to examine the principles of human transcriptional regulatory networks; the results are integrated with other genomic information to form a hierarchical meta-network where different levels have distinct properties.

    • Mark B. Gerstein
    • , Anshul Kundaje
    •  & Michael Snyder
  • Review Article |

    Over the past ten years, protein engineering has established biocatalysis as a practical and environmentally friendly alternative to traditional forms of catalysis both in the laboratory and in industry.

    • U. T. Bornscheuer
    • , G. W. Huisman
    •  & K. Robins
  • Article |

    Thousands of quorum-sensing Escherichia coli colonies are synchronized over centimetres using redox signalling to create ‘biopixels’ that can sense trace amounts of arsenic in water.

    • Arthur Prindle
    • , Phillip Samayoa
    •  & Jeff Hasty
  • Letter |

    For synthetic biologists' creativity to be unleashed, basic circuits must become truly interchangeable, that is, modular and scalable. This study, one of two linked papers, has harnessed bacterial 'quorum sensing' to achieve complex computation through communication between individual cells performing simple logic functions. Such extracellular 'chemical wiring' is one promising way to get around intracellular noise when building more complex genetic circuitry.

    • Alvin Tamsir
    • , Jeffrey J. Tabor
    •  & Christopher A. Voigt
  • Article |

    The central amygdala relies on inhibitory circuitry to encode fear memories, but how this information is acquired and expressed in these connections is unknown. Two new papers use a combination of cutting-edge technologies to reveal two distinct microcircuits within the central amygdala, one required for fear acquisition and the other critical for conditioned fear responses. Understanding this architecture provides a strong link between activity in a specific circuit and particular behavioural consequences.

    • Wulf Haubensak
    • , Prabhat S. Kunwar
    •  & David J. Anderson
  • Letter |

    Although new amino acids with desirable properties can be devised, only a few have been successfully introduced into proteins by the cellular machinery. Even then, only one type of unnatural amino acid can be added to a given protein. Here, a new system has been designed that could allow the incorporation of up to 200 novel amino acids. The system involves an orthogonal ribosome that uses quadruplet — rather than triplet — codons, as well as orthogonal tRNA synthetase–tRNA pairs.

    • Heinz Neumann
    • , Kaihang Wang
    •  & Jason W. Chin
  • Article |

    A defining focus of synthetic biology is the engineering of genetic circuits with predictive functionality in living cells. Here, a decade after the first synthesized genetic toggle switch and oscillator, an engineered gene network with global intercellular coupling is designed that is capable of generating synchronized oscillations in a growing population of cells.

    • Tal Danino
    • , Octavio Mondragón-Palomino
    •  & Jeff Hasty