• Article |

    Strand-specific RNA-seq (ssRNA-seq) data often lack information on 5′ and 3′ ends of transcripts. Here the authors present a novel method for ssRNA-seq that enables the simultaneous profiling of gene expression, TSSs and polyadenylation sites at near-base resolution with a single library.

    • Saurabh Agarwal
    • , Todd S. Macfarlan
    •  & Shigeki Iwase
  • Article |

    Direct cell–cell interactions form the basis of the adaptive immune response. Here, Dura et al.present an advanced microfluidic platform that enables highly parallel pairing of primary immune cells and multiparametric and dynamic measurements of lymphocyte interactions and activation processes.

    • Burak Dura
    • , Stephanie K. Dougan
    •  & Joel Voldman
  • Article
    | Open Access

    The correct assembly of genomes from sequencing data remains a challenge due to difficulties in correctly assigning the location of repeated DNA elements. Here the authors describe GRAAL, an algorithm that utilizes genome-wide chromosome contact data within a probabilistic framework to produce accurate genome assemblies.

    • Hervé Marie-Nelly
    • , Martial Marbouty
    •  & Romain Koszul
  • Article |

    Pentatricopeptide repeat (PPR) proteins bind RNA and control diverse aspects of RNA metabolism in eukaryotic cells. Here, Coquille et al.present the crystal structures of several engineered PPR domains, elucidate their RNA binding mode and suggest paths to the design of modular, sequence-specific PPR domains.

    • Sandrine Coquille
    • , Aleksandra Filipovska
    •  & Oliver Rackham
  • Article |

    Molecular and functional differences between induced pluripotent stem cells (iPSCs) derived from distinct cell types have been described. Here the authors show, by comparing human iPSCs derived from fibroblasts or cord blood, that the competence in activating developmental genes upon differentiation is influenced by the donor cell of origin.

    • Jong-Hee Lee
    • , Jung Bok Lee
    •  & Mickie Bhatia
  • Article |

    Genome editing has yet to be performed in non-bilaterian phyla. Here, Ikmi et al. develop techniques to use both TALEN and CRISPR/Cas9 in the sea anemone, Nematostella vectensis, and further leverage a locus expressing an endogenous fluorescent protein as a landing site for homologous recombination-mediated transgenesis.

    • Aissam Ikmi
    • , Sean A. McKinney
    •  & Matthew C. Gibson
  • Article
    | Open Access

    Brain–machine interfaces offer the possibility of controlling prosthetic devices using changes in brain activity. Folcher et al.couple such a system wirelessly to an optogenetic implant in mice to control expression of a transgene, demonstrating its potential for mind-controlled drug delivery.

    • Marc Folcher
    • , Sabine Oesterle
    •  & Martin Fussenegger
  • Article |

    The death receptor CD95/Fas induces apoptosis of many normal cells but prevents necrotic death of cancer cells. Here the authors demonstrate that CD95 activation promotes a cancer stem cell (CSC) phenotype, and that CSCs but not differentiated cancer cells are resistant to CD95-mediated apoptosis and depend on CD95 signalling to prevent necrosis.

    • Paolo Ceppi
    • , Abbas Hadji
    •  & Marcus E. Peter
  • Article |

    The development of software tools to analyse large mass spectrometry data sets lags behind the increase in diversity of the data. Here the authors develop MS-GF+, a database search tool that outperforms other popular tools in identifying peptides from a variety of data sets.

    • Sangtae Kim
    •  & Pavel A. Pevzner
  • Article |

    The availability of tracers to track the health of cells over long periods of time will be of value to optimize cell-based therapy. Here, Lee et a nanoparticle that fluoresces red in living cells, but fluoresces green when cells begin to die from apoptosis or necrosis.

    • Seung Koo Lee
    • , Luke J. Mortensen
    •  & Ching-Hsuan Tung
  • 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 |

    Magneto-fluorescent nanoparticles hold promise for bioimaging applications, but synthesizing uniform particles with tunable sizes remains challenging. Chen et al. propose an approach for co-assembling magnetic particles with fluorescent quantum dots, leading to well-defined core-shell structures.

    • Ou Chen
    • , Lars Riedemann
    •  & Moungi G. Bawendi
  • Article
    | Open Access

    Next-generation sequencing technology has made the generation of huge amounts of genetic data possible, but phenotype characterization remains slow and difficult. Here the authors develop a high-throughput phenotyping facility for rice that is able to accurately identify and characterize traits related to morphology, biomass and yield.

    • Wanneng Yang
    • , Zilong Guo
    •  & Lizhong Xiong
  • Article |

    Toggle switches can be engineered using pairs of transcriptional repressors; however, their bistability depends on nonlinear DNA-binding properties. Lebar et al. design a circuit that ensures bistability by artificially generating nonlinearity and use it to construct a toggle from programmable DNA-binding domains.

    • Tina Lebar
    • , Urban Bezeljak
    •  & Roman Jerala
  • Article |

    Bacterial cells use a self-generated extracellular matrix of various biomolecules in order to form biofilms and promote their stability. Here, the authors present a method for genetically controlling the composition of this extracellular matrix to yield more functional biofilms.

    • Peter Q. Nguyen
    • , Zsofia Botyanszki
    •  & Neel S. Joshi
  • Article
    | Open Access

    Cell therapy requires sufficient amounts of therapeutic cells to be delivered to the injured tissue. Here the authors use magnetic iron nanoparticles conjugated with antibodies that bind therapeutic cells and cardiomyocytes to treat myocardial ischemia/reperfusion injury in rats and show that targeting to the heart is enhanced upon local application of a magnetic field.

    • Ke Cheng
    • , Deliang Shen
    •  & Eduardo Marbán
  • Article
    | Open Access

    Protein unfolding and translocation through membrane pores occurs in several biological processes and has implications in nanopore technologies. Here, the authors show that the kinetics of unfolding differ depending on which end of the chain enters the pore first.

    • David Rodriguez-Larrea
    •  & Hagan Bayley
  • Article |

    Current leukocyte migration assays usually report bulk attractive behaviour of cells within a chemokine gradient. Here, the authors develop a microfluidic device to simultaneously measure several migration responses on exposure to commonly used leukocyte chemokines, and report previously unrecognized cell behaviour.

    • Leo Boneschansker
    • , Jun Yan
    •  & Daniel Irimia
  • Article
    | Open Access

    Propane is the main component of liquid petroleum gas and has a wide variety of commercial applications. Here, the authors engineer a synthetic metabolic pathway in E. coli, and demonstrate for the first time the renewable production of propane.

    • Pauli Kallio
    • , András Pásztor
    •  & Patrik R. Jones
  • Article
    | Open Access

    Common methods to detect adenosine-to-inosine RNA editing sites rely on mapping short RNA reads to the genome while allowing only a limited number of mismatches. Here, Porath et al. present a novel RNA-seq based approach to identify hyper-edited reads that significantly expands the RNA editome.

    • Hagit T. Porath
    • , Shai Carmi
    •  & Erez Y. Levanon
  • Article |

    Nanoparticles can be used for therapeutic and diagnostic purposes. Here, the authors report that nanoparticles made of a single chemical building block, called nanoporphyrins, incorporate eight different functionalities, including various types of imaging, drug delivery and cancer therapy.

    • Yuanpei Li
    • , Tzu-yin Lin
    •  & Kit S. Lam
  • Article |

    Optimizing cell-surface biological reactions is an important goal of biotechnology and industrial processes. Here the authors use macromolecular crowding to enhance the enzymatic conversion of red blood cells to the universal type O blood type, using orders of magnitude less enzyme than was previously required.

    • Rafi Chapanian
    • , David H. Kwan
    •  & Jayachandran N Kizhakkedathu
  • Article |

    Current CRISPR-mediated genome-editing methods are limited by the requirement for a specific +1 nucleotide when using the U6 promoter to drive guide RNA synthesis. Now, Ranganathan et a modification of the CRISPR–Cas9 system that more than doubles the number of targetable CRISPR sites within the human genome.

    • Vinod Ranganathan
    • , Karl Wahlin
    •  & Donald J. Zack
  • Article |

    The amino acid, L-arginine, has important applications in the food, pharmaceutical and cosmetics industries. Here the authors systematically engineer a Corynebacterium glutamicum strain for the production of L-arginine, and show that their metabolic engineering approach can be used for the industrial production of valuable chemicals.

    • Seok Hyun Park
    • , Hyun Uk Kim
    •  & Sang Yup Lee
  • Article
    | Open Access

    The advancement of sensitive, accurate and non-invasive methods to identify the allergen that drives allergic disease in an individual remains a challenge. Here, the authors develop a synthetic biology approach using human designer cells to profile allergic reactions against an array of allergens measuring histamine release from whole blood.

    • David Ausländer
    • , Benjamin Eggerschwiler
    •  & Martin Fussenegger
  • 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 |

    The incorporation of foreign objects into cells can be used in various avenues of biological research, although crossing the cell membrane can be challenging. Here, the authors use a diamond nanoneedle array for enhanced delivery of various particles into cells, including neurons.

    • Ying Wang
    • , Yang Yang
    •  & Peng Shi
  • Article |

    Antibody–antigen recognition is one of the important aspects of immunity, but the nanomechanical process of this recognition is not fully understood. Here, using high-speed atomic force microscopy, the authors observe that on membranes containing a high density of immobile antigens antibodies move in a ‘random walking’ motion.

    • Johannes Preiner
    • , Noriyuki Kodera
    •  & Peter Hinterdorfer
  • Article
    | Open Access

    Graphene’s properties are well known, but turning this atomically thin material into three-dimensional devices remains a challenge. Here, the authors report an assembly process for chemically modified graphene into three-dimensional cellular networks, with control over the physical properties of the resulting materials.

    • Suelen Barg
    • , Felipe Macul Perez
    •  & Eduardo Saiz
  • Article |

    Nucleic acids possess a number of properties that can be beneficial for the fabrication of nanomaterials. Here, the authors present an enzymatically synthesised RNA membrane, and show how its physical properties can be controlled by changes to base-pairing.

    • Daehoon Han
    • , Yongkuk Park
    •  & Jong Bum Lee
  • Article |

    The study of cell membrane proteins can be simplified by incorporating them into lipid bilayers, but doing this for multiple proteins can be challenging. Here, the authors present a technique to achieve this, and show reconstitution of a bacterial respiratory chain from individual components.

    • Gustav Nordlund
    • , Peter Brzezinski
    •  & Christoph von Ballmoos
  • Article |

    Many tissues can be grown as 3D spheroid models in hanging drops of media. Here, Frey et al. develop a microfluidic, interconnected hanging drop network to facilitate inter-drop communication, and demonstrate that pro-drug conversion by liver spheroids can limit the growth of cancer spheroids in adjacent drops.

    • Olivier Frey
    • , Patrick M. Misun
    •  & Andreas Hierlemann
  • Article |

    Robust and reliable structure–function relationships are valuable for the development of potent drug delivery systems. Here, the authors use a library of lipid-like materials to predict in vivosiRNA delivery efficacy without any biological testing.

    • Kathryn A. Whitehead
    • , J. Robert Dorkin
    •  & Daniel G. Anderson
  • Article |

    Gramicidin A pores are important natural structures for the transport of ions through biological membranes. Here, the authors show that this functionality can be mimicked using an artificial transmembrane channel formed of synthetic pore-forming compounds.

    • Mihail Barboiu
    • , Yann Le Duc
    •  & Thomas Fyles
  • Article |

    Ganglioside GM3, a cellular lipid included in the envelope of HIV-1 viral particles, interacts with cellular receptor CD169. Here, the authors develop artificial nanoparticles, consisting of a golden core and a GM3-containing synthetic membrane, that recapitulate the CD169-dependent uptake of viral particles.

    • Xinwei Yu
    • , Amin Feizpour
    •  & Björn M. Reinhard
  • Article
    | Open Access

    Vanilla is derived from vanillin isolated from a vanillin-producing orchid, but the process is laborious, costly and results in a small yield. Here, the authors identified an enzyme from the orchid, Vanilla planifolia, that is able to catalyse the formation of vanillin and vanillin glucoside from ferulic acid and its glucoside in vitro, respectively.

    • Nethaji J. Gallage
    • , Esben H. Hansen
    •  & Birger Lindberg Møller
  • Article
    | Open Access

    Extreme reproductive sex ratios could result in the suppression or elimination of pest populations. Here, the authors design a synthetic sex distortion system in Anopheles gambiaethat gives rise to fertile mosquito strains that produce over 95% male offsprings and could therefore be used to suppress mosquito populations.

    • Roberto Galizi
    • , Lindsey A. Doyle
    •  & Andrea Crisanti