• Article
    | Open Access

    Super-resolution imaging of microtubules requires labels that increase their apparent diameter, making it difficult to resolve individual microtubules within a bundle. Here, the authors develop single-chain antibody fragments against tubulin that enable closely spaced individual microtubules to be distinguished in cells.

    • Marina Mikhaylova
    • , Bas M. C. Cloin
    •  & Lukas C Kapitein
  • Article
    | Open Access

    Antisense oligonucleotides (ASOs) can repress the expression of specific genes. Here, the authors show that a DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from ASOs is more potent in suppressing target gene expression, and causes a less adverse effect in mouse liver.

    • Kazutaka Nishina
    • , Wenying Piao
    •  & Takanori Yokota
  • Article
    | Open Access

    Monoclonal antibodies with broadly neutralizing activity are being developed as potential treatment of influenza infections. Here, the authors describe a broadly neutralizing antibody with an unusual mode of binding to viral haemagglutinin, which has been isolated from patients convalescent from pandemic H1N1 influenza infection.

    • Ying Wu
    • , MyungSam Cho
    •  & Ruben O. Donis
  • Article
    | Open Access

    Endogenous fungal gene promoters can be hundreds of base pairs long, limiting their use in synthetic biology and biotechnology. Here Redden and Alper screen a library of synthetic promoter elements to generate compact DNA sequences of 100 base pairs able to drive high levels of gene expression.

    • Heidi Redden
    •  & Hal S. Alper
  • Article
    | Open Access

    Organogenesis is orchestrated by biochemical and biophysical stimuli. Here, Ma et al. generate a micro-patterned surface that provides mechanical cues which, when combined with biochemical signals, drive human pluripotent stem cells’ differentiation into beating cardiac microchambers resembling primitive hearts.

    • Zhen Ma
    • , Jason Wang
    •  & Kevin E. Healy
  • Article
    | Open Access

    Synthetic engineering of complex pathways is often hindered by pathway branching and generation of non-target compounds. Here, the authors show that by judicious combination of moderately selective enzyme variants, a non-natural C50 carotenoid can be generated in bacteria with minimal production of unwanted compounds.

    • Maiko Furubayashi
    • , Mayu Ikezumi
    •  & Daisuke Umeno
  • Article |

    Telodendrimers are versatile and robust nanoparticle-based drug carriers. From a screen of potential small-molecule building blocks, Shi et al.identify rhein-containing telodendrimers as stable and effective nanocarriers of doxorubicin for treating a xenograft Raji lymphoma model.

    • Changying Shi
    • , Dandan Guo
    •  & Juntao Luo
  • Review Article |

    There are many examples in nature of biological materials having developed interesting mechanical properties to enhance their functional performance. Here, Egan et al. review these materials and how they can inspire the design of biomimetic mechanical systems.

    • Paul Egan
    • , Robert Sinko
    •  & Sinan Keten
  • Article
    | Open Access

    Achieving high carbon yields is crucial for biotechnological production of metabolites in engineered microorganisms. Here, Tashiroet al. generate E. colistrains that produce acetyl-CoA and a derived metabolite (isobutyl acetate) in the absence of pyruvate decarboxylation, leading to increased carbon yields.

    • Yohei Tashiro
    • , Shuchi H. Desai
    •  & Shota Atsumi
  • Article
    | Open Access

    The investigation of the chemical reactivity of metal centres in metalloproteins in aqueous solution is challenging. Here, the authors demonstrate the use of single molecule force spectroscopy to study the chemical reactivity of the iron-sulfur centre in rubredoxin in aqueous solution.

    • Peng Zheng
    • , Guilherme M. Arantes
    •  & Hongbin Li
  • Article
    | Open Access

    Avoiding central cell necrosis at the centre of large engineered tissue constructs is an important issue forin vitrotissue engineering. Here, the authors demonstrate that this problem may be overcome by oxygenating human mesenchymal stem cells with artificial membrane-binding proteins.

    • James P. K. Armstrong
    • , Rameen Shakur
    •  & Anthony P. Hollander
  • Article
    | Open Access

    Familial hypercholesterolemia (FH) is a congenital disease associated with high plasma cholesterol levels. Here, the authors recapitulate FH in chimeric mice, in which livers are repopulated with hepatocytes from an FH patient, and successfully correct the disease using adenovirus-mediated gene therapy.

    • Beatrice Bissig-Choisat
    • , Lili Wang
    •  & Karl-Dimiter Bissig
  • Article
    | Open Access

    Bacterial DNA methylation is involved in many processes, from host defense to antibiotic resistance, however current methods for examining methylated genomes lack single-cell resolution. Here Beaulaurier et al. present Single Molecule Modification Analysis of Long Reads, a new tool for de novodetection of epigenetic heterogeneity.

    • John Beaulaurier
    • , Xue-Song Zhang
    •  & Gang Fang
  • Article
    | Open Access

    Proximity ligation assays are a sensitive method for detecting protein interactions, but require the addition of enzymes. Here the authors introduce proxHCR, an enzyme-free method of detecting interactions in close proximity by inducing a hybribization chain reaction (HCR) of fluorescently labelled oligonucleotides.

    • Björn Koos
    • , Gaëlle Cane
    •  & Ola Söderberg
  • Article
    | Open Access

    DNA phasing information — the determination of which specific sequences belong to the same DNA molecule—is not easily obtained from sequencing applications that rely on short reads. Here the authors develop a phasing method based on massively parallel barcoding of single DNA molecules.

    • Erik Borgström
    • , David Redin
    •  & Afshin Ahmadian
  • Article
    | Open Access

    Adverse drug reactions are an important clinical problem. Here the authors combine information about drug-induced gene expression changes and genetic variability of patients with a genome-scale metabolic model to identify drug-induced changes in cellular metabolism that may be linked to drug side effects.

    • Daniel C. Zielinski
    • , Fabian V. Filipp
    •  & Bernhard O. Palsson
  • Article
    | Open Access

    The ability to contain and destroy synthetically engineered microorganisms is an important consideration with environmental, industrial and intellectual property implications. Here Caliando et al. design and demonstrate a stably integrated CRISPR-based system for targeted DNA destruction.

    • Brian J. Caliando
    •  & Christopher A. Voigt
  • Article
    | Open Access

    Retinal-bound opsins are widely used tools for optical control of neuronal activity in vivo, so called optogenetics. Here, using molecular simulations, biochemistry, electrophysiology and X-ray crystallography, the authors present new molecular design principles for the generation of blue-shifted variants of microbial rhodopsins.

    • Hideaki E. Kato
    • , Motoshi Kamiya
    •  & Osamu Nureki
  • Article
    | Open Access

    Screening genomic or metagenomic libraries for interesting products or activities is often hampered by poor gene expression in a heterologous host. Here the authors show that the expression of a Lactobacillus sigma factor greatly enhances transcription of heterologous and environmental DNA in E. coli.

    • Stefan M. Gaida
    • , Nicholas R. Sandoval
    •  & Eleftherios T. Papoutsakis
  • Article |

    Hydrogels are commonly used materials for tissue engineering, but they can lack the structural properties required for load-bearing and mechanical applications. Here, the authors prepare a polycaprolactone scaffold using melt-electrospinning to reinforce a gelatin methacrylamide hydrogel.

    • Jetze Visser
    • , Ferry P.W. Melchels
    •  & Jos Malda
  • Article |

    cAMP is a second messenger that acts in distinct intracellular locations regulating diverse cellular functions. Here the authors design a FRET-based cAMP biosensor and use it to measure in vivodynamics of cAMP concentration changes in the sarcoplasmatic reticulum of mouse cardiomyocytes in health and disease.

    • Julia U. Sprenger
    • , Ruwan K. Perera
    •  & Viacheslav O. Nikolaev
  • Article |

    Cystic fibrosis is a lethal genetic disorder commonly caused by the F508del mutation which is not amenable to gene therapy. Here, the authors use triplex-forming PNA molecules and donor DNA in biodegradable polymer nanoparticles to correct F508del and achieve clinically relevant levels of gene editing.

    • Nicole Ali McNeer
    • , Kavitha Anandalingam
    •  & Marie E. Egan
  • Article |

    Protein switches have a number of potential biotechnological applications. Here, the authors present fusions of maltose-binding protein with TEM1 β-lactamase as multi-input allosteric protein switches that can be controlled by temperature and pH in the presence of the effector.

    • Jay H. Choi
    • , Abigail H. Laurent
    •  & Marc Ostermeier
  • Article
    | Open Access

    Algae hold great promise for biofuel and chemical production but their use as model systems is hampered by the absence of suitable genetic tools. Here Karas et al. present a nuclear episomal vector for diatoms that is maintained in the absence of antibiotics, and a plasmid delivery method via conjugation with E. coli.

    • Bogumil J. Karas
    • , Rachel E. Diner
    •  & Philip D. Weyman
  • Article |

    Characterizing mammalian gene expression regulation by enhancer elements is complicated by the size and complexity of the genome. Here Vanhille et al.demonstrate CapStarr-Seq, a novel high-throughput method for assessing potential enhancers and deciphering the mechanisms regulating transcription

    • Laurent Vanhille
    • , Aurélien Griffon
    •  & Salvatore Spicuglia
  • Article
    | Open Access

    Antibody–drug conjugates are a class of therapeutic combining the directing ability of antibodies with the cell-killing ability of cytotoxic drugs. Here the authors describe an approach based on click chemistry that enables the rapid assembly of dual-modified antibodies with potential for new therapeutic modalities.

    • Antoine Maruani
    • , Mark E.B. Smith
    •  & Stephen Caddick
  • Article
    | Open Access

    It is known that skin has a large tear resistance, but little is known of the mechanism behind this. Here, the authors carry out a structural analysis of rabbit skin to show how the deformation of collagen fibrils in the skin results in a strong resistance to tear propagation.

    • Wen Yang
    • , Vincent R. Sherman
    •  & Marc A. Meyers
  • Article |

    Electrospinning is a useful method of biomaterial fabrication, but a lack of bioactivity in the final construct can limit their application as mimics for biological matrices. Here, the authors fabricate a degradable electrospun scaffold as an in vitro and in vivomimic of the extracellular matrix.

    • Ryan J. Wade
    • , Ethan J. Bassin
    •  & Jason A. Burdick
  • Article
    | Open Access

    Some oligomers exhibit liquid-crystal-like ordering in concentrated aqueous solutions. Here, Fraccia et al. show that this kind of ordering can further facilitate DNA ligation in a way similar to a catalytic process that arises from a hierarchical self-assembly, namely liquid crystal autocatalysis.

    • Tommaso P. Fraccia
    • , Gregory P. Smith
    •  & Tommaso Bellini
  • Article
    | Open Access

    Photosynthetic reaction centres have been proposed for applications in bioelectronics. Here, the authors examine electron transport through the reaction centre from R. sphaeroidesusing conductive AFM, observing asymmetric conductance along only one cofactor wire under an applied bias.

    • Muhammad Kamran
    • , Vincent M. Friebe
    •  & Michael R. Jones
  • Article
    | Open Access

    Efficacy of anticancer treatments vary across patients, imposing a need for personalized approaches. Here the authors show that responsiveness to chemotherapy can be predicted using tumour explant cultures in a patient-matched microenvironment, coupled with a machine-learning algorithm.

    • Biswanath Majumder
    • , Ulaganathan Baraneedharan
    •  & Pradip K. Majumder
  • Article |

    Recombination-based tools for generating targeted mutations in Mycobacterium tuberculosislack efficiency. Here the authors present a CRISPR interference approach that is able to efficiently repress the expression of target genes in mycobacteria, in a rapid and cost-effective manner.

    • Eira Choudhary
    • , Preeti Thakur
    •  & Nisheeth Agarwal
  • Article |

    Photoreceptor-based photoswitches have proved to be powerful tools for the specific control of protein activity in live cells. Here the authors describe Magnets, a new set of photoswitches based on the Vivid photoreceptor with enhanced hetero-dimerization specificity and variable activation kinetics.

    • Fuun Kawano
    • , Hideyuki Suzuki
    •  & Moritoshi Sato
  • Article
    | Open Access

    Epigenetic changes associated with post-natal differentiation have been characterized. Here the authors generate epigenomic and transcriptional profiles from primary human breast cells, providing insights into the transcriptional and epigenetic events that define post-natal cell differentiation in vivo.

    • Philippe Gascard
    • , Misha Bilenky
    •  & Martin Hirst
  • Article
    | Open Access

    Protein phosphorylation is known to play an important role in cell adhesion signalling. Robertson et al. present a proteomic resource mapping the phosphorylation states of proteins isolated from adhesion complexes and, taking advantage of this data set, show that the cell cycle kinase CDK1 may influence cell adhesion.

    • Joseph Robertson
    • , Guillaume Jacquemet
    •  & Martin J. Humphries
  • Article
    | Open Access

    The degradation of materials used in biological applications has an important bearing on their long term performance. Here, the authors show how porous silicon nanoparticle degradation can be accelerated in vivothrough the influence of local tissue pathology, likely influencing drug delivery performance.

    • Adi Tzur-Balter
    • , Zohar Shatsberg
    •  & Natalie Artzi
  • Article |

    The clinical use of adeno-associated virus vectors (AAVs) has been limited by the lack of transduction specificity. Here the authors show that receptor-targeted, affinity-tagged, and purified AVVs reach tumours in mouse models with high selectivity and efficiency, outperforming therapeutic antibodies.

    • Robert C. Münch
    • , Anke Muth
    •  & Christian J. Buchholz
  • Article |

    Microbial formate dehydrogenases (FDH) are molybdenum-containing enzymes that can catalyse the reduction of CO2 into formate. Here, the authors suggest a structural and functional basis for sulphuration of the molybdenum cofactor in E. coliFDH, a key step in the production of active formate dehydrogenase.

    • Pascal Arnoux
    • , Christian Ruppelt
    •  & Anne Walburger