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Article |
Design of synthetic yeast promoters via tuning of nucleosome architecture
Model-based part design is a key step in synthetic biology. Here, the authors report a method for tuning nucleosome architecture in order to strengthen native promoters and facilitate synthetic promoter design in yeast.
- Kathleen A. Curran
- , Nathan C. Crook
- & Hal S. Alper
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Article |
An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging
Infrared fluorescent proteins offer advantages for deep in vivo imaging thanks to the tissue-penetrating properties of infrared light. Here, Yu et al. design a monomeric infrared fluorescent protein that, when combined with expression of haeme oxygenase in cells, shows improved performance for in vivoimaging of neurons and brain tumours.
- Dan Yu
- , William Clay Gustafson
- & Xiaokun Shu
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Article |
Protein grafting of p53TAD onto a leucine zipper scaffold generates a potent HDM dual inhibitor
The protein levels of the tumour suppressor p53 can be negatively regulated by HDM2, which is an attractive target for cancer therapy. In this study, Lee et al. graft the transactivation domain of p53 onto a scaffold protein and show that this binds to HDM2 and inhibits cancer cell growth in vitro.
- Jung-Hoon Lee
- , Eunji Kang
- & Jae Il Lee
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Article |
Macromolecular structures probed by combining single-shot free-electron laser diffraction with synchrotron coherent X-ray imaging
Macromolecular complexes hold promise for future generations of drug delivery carriers, but probing their structures with high resolution is challenging. Here, the authors combine X-ray free-electron laser and synchrotron approaches to reveal the core-shell structure of RNA interference microsponges.
- Marcus Gallagher-Jones
- , Yoshitaka Bessho
- & Changyong Song
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Article
| Open AccessThe emerging biofuel crop Camelina sativa retains a highly undifferentiated hexaploid genome structure
Camelina sativa is an oilseed crop with important industrial applications. Here, the authors sequence the C. sativagenome to investigate the genome organization and evolution of this species, and to provide a valuable tool for genetic engineering and potential crop improvement.
- Sateesh Kagale
- , Chushin Koh
- & Isobel A. P. Parkin
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Article
| Open AccessExperimental orthotopic transplantation of a tissue-engineered oesophagus in rats
Patients with oesophageal diseases may require surgical removal and replacement of the oesophagus. Here the authors seed mesenchymal stromal cells on a decellularized rat oesophagus and show that this bioengineered tissue construct restores swallowing function after transplantation into rats.
- Sebastian Sjöqvist
- , Philipp Jungebluth
- & Paolo Macchiarini
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Article |
Tyrosine-mediated two-dimensional peptide assembly and its role as a bio-inspired catalytic scaffold
It is well known that the interplay between molecular ordering and interface geometry can determine the morphology of two-dimensional systems. Here, the authors report facet formation in water droplets, driven by peptide assembly, and investigate the structural and sequence motifs that affect this behaviour.
- Hyung-Seok Jang
- , Jung-Ho Lee
- & Yoon-Sik Lee
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Article
| Open AccessThe seco-iridoid pathway from Catharanthus roseus
The (seco)iridoids and their monoterpenoid indole alkaloid (MIA) derivatives are plant-derived compounds with pharmaceutical applications. Here, the authors identify the last four missing steps of the (seco)iridoid pathway, which they reconstitute in an alternative plant host to produce the complex MIA, strictosidine.
- Karel Miettinen
- , Lemeng Dong
- & Danièle Werck-Reichhart
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Article |
Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer
Light-controlled mechanisms for the delivery of drug molecules to cells is a promising route for non-invasive disease therapy. Here, the authors develop a photosensitive polymeric micelle for light-induced gene transfection and show its effectiveness in vivovia systemic administration.
- Takahiro Nomoto
- , Shigeto Fukushima
- & Kazunori Kataoka
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Article
| Open AccessAn auto-inducible mechanism for ionic liquid resistance in microbial biofuel production
Ionic liquids (ILs) are important solvents in the microbial production of biofuels, but can inhibit microbial growth. Here, the authors transfer newly discovered IL-resistance genes from rain forest soil bacteria to E. coliand report growth and biofuel production at IL levels that are otherwise toxic to native strains.
- Thomas L. Ruegg
- , Eun-Mi Kim
- & Michael P. Thelen
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Article |
Microfluidic probe for single-cell analysis in adherent tissue culture
Cellular heterogeneity is a feature of diverse disease processes, yet is masked in typical biochemical assays. Sarkar et al.develop a microfluidic device to access the contents of single cells in adherent culture, allowing biochemical measurements to be connected with phenotypic information.
- Aniruddh Sarkar
- , Sarah Kolitz
- & Jongyoon Han
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Article |
Bio-barcode gel assay for microRNA
MicroRNA has been identified to play a role in cancer development, thus its detection at low concentrations would be a highly beneficial diagnostic tool. Here, the authors develop a gel-based bio-barcode assay for microRNA detection using DNA-modified gold nanoparticles, with aM limits of detection.
- Hyojin Lee
- , Jeong-Eun Park
- & Jwa-Min Nam
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Article
| Open AccessA plant factory for moth pheromone production
Pheromones can be used as an environmentally friendly alternative to traditional pesticides. Here, the authors produce moth sex pheromones in Nicotiana benthamianaby transient expression and demonstrate that these pheromones are able to trap male moths as efficiently as their synthetic counterparts.
- Bao-Jian Ding
- , Per Hofvander
- & Christer Löfstedt
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Article |
Microgels on-demand
Traditional methods for forming hydrogel particles are limited by geometry and lack of addressability after synthesis. Here the authors use digital microfluidics to form individually addressable gels with customisable shapes and compositions.
- Irwin A. Eydelnant
- , Bingyu Betty Li
- & Aaron R. Wheeler
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Article |
A cortical–spinal prosthesis for targeted limb movement in paralysed primate avatars
Brain–machine interfaces are being investigated for recovery of motor function after paralysis. Shanechi et al.present a neural prosthesis that decodes premotor neuronal activity in an alert monkey to activate spinal neurons and muscles that produce target-directed movements in a sedated monkey or avatar.
- Maryam M. Shanechi
- , Rollin C. Hu
- & Ziv M. Williams
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Article |
Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography
Serial femtosecond X-ray crystallography permits the use of very small protein crystals; however, a continuous flow of sample is required. Weierstall et al. design and demonstrate an injector system that can supply microcrystals in the lipidic cubic phase, dramatically reducing the quantities of protein required.
- Uwe Weierstall
- , Daniel James
- & Vadim Cherezov
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Article |
Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae
Benzylisoquinoline alkaloids are a group of plant secondary metabolites with important pharmaceutical applications. Here, the authors have reconstituted a 10-gene alkaloid pathway in Saccharomyces cerevisiae, demonstrating the feasibility of producing commercially important alkaloids in microbial systems.
- Elena Fossati
- , Andrew Ekins
- & Vincent J. J. Martin
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Article |
Photoautotrophic hydrogen production by eukaryotic microalgae under aerobic conditions
Eukaryotic algae and cyanobacteria can produce hydrogen in the presence of little or no oxygen. Here, the authors show that two microalgal strains are capable of producing hydrogen under aerobic conditions, and provide new insights into the natural evolution of oxygen-tolerant hydrogenase.
- Jae-Hoon Hwang
- , Hyun-Chul Kim
- & Byong-Hun Jeon
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Article |
Synthetic polymers enable non-vitreous cellular cryopreservation by reducing ice crystal growth during thawing
Cryopreservation is the method of choice for extending the lifespan of biological samples, although high concentrations of potentially toxic additives are required. Here, the authors show that polymers that mimic antifreeze proteins can enhance cell cryopreservation at only 0.1 wt% concentration.
- Robert C. Deller
- , Manu Vatish
- & Matthew I. Gibson
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Article |
Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells
The hair follicle bulge contains epithelial stem cells that contribute to follicle formation during each hair cycle. Here the authors differentiate human induced pluripotent stem cells into folliculogenic epithelial stem cells, which can produce all hair follicle lineages including a stem cell population.
- Ruifeng Yang
- , Ying Zheng
- & Xiaowei Xu
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Article |
Biomimetic virus-based colourimetric sensors
Colour changes in response to external stimuli are common in nature, from turkey skin to butterfly wings. Here, inspired by this behaviour, the authors have developed a sensor capable of providing an individual colour response to specific target chemicals using genetically engineered viruses.
- Jin-Woo Oh
- , Woo-Jae Chung
- & Seung-Wuk Lee
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Article |
Genotyping with CRISPR-Cas-derived RNA-guided endonucleases
Cas9 RNA-guided engineered nucleases (RGENs) induce site-specific DNA cleavages in cultured cells and organisms and are used widely as genome-editing tools. Here, the authors develop an RGEN-based technology to genotype both RGEN-induced mutations and cancer-associated mutations in human cell lines.
- Jong Min Kim
- , Daesik Kim
- & Jin-Soo Kim
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Article |
Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production
Bio-based production of oils and lipids could potentially provide a sustainable fuel alternative to petroleum. Here, the authors show that Yarrowia lipolytica’s metabolism can be rewired to saturate cells with upwards of 90% lipid content and significantly increase lipid production.
- John Blazeck
- , Andrew Hill
- & Hal S. Alper
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Article |
A self-propelled biohybrid swimmer at low Reynolds number
Self-propelled biological microswimmers in viscous fluids are common in nature, but their synthetic counterparts are not available to date. Williams et al.develop a hybrid swimmer to emulate flagellar propulsion, which provides a platform to add engineered functionality to complex motile devices.
- Brian J. Williams
- , Sandeep V. Anand
- & M. Taher A. Saif
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Article |
A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios
Polymers represent promising gene vectors due to their high efficiency and low cytotoxicity. Here, the authors show that fluorination increases gene transfection efficacy, while reducing cytotoxicity, and suggest an important role for this strategy in the design of efficient gene vectors.
- Mingming Wang
- , Hongmei Liu
- & Yiyun Cheng
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Article |
A fully genetically encoded protein architecture for optical control of peptide ligand concentration
The design of optogenetic tools to control ion channel function typically requires careful consideration of channel structure. Schmidt et al. present a modular strategy to engineer light sensitivity in several K+channels, which functions independently of exogenous chemical modulators.
- Daniel Schmidt
- , Paul W. Tillberg
- & Edward S. Boyden
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Article |
High efficiency cell-specific targeting of cytokine activity
Despite their clinical potential, cytokines can often be highly toxic in patients, due to their systemic activity. Here, the authors present a strategy to engineer immunocytokines with very high targeting efficacies using mutant cytokines linked to nanobodies that only become active when bound to a specific cell marker.
- Geneviève Garcin
- , Franciane Paul
- & Gilles Uzé
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Article
| Open AccessUltrashort single-walled carbon nanotubes in a lipid bilayer as a new nanopore sensor
Nanopore sensors are a promising tool for the controlled detection of a range of possible substrates. Here the authors describe a nanopore sensor based on short single-walled carbon nanotubes inserted into a lipid bilayer, with modified sensing properties compared to longer nanotubes.
- Lei Liu
- , Chun Yang
- & Hai-Chen Wu
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Article |
Engineering protein thermostability using a generic activity-independent biophysical screen inside the cell
Methods to improve protein stability are important in the biopharmaceutical industry. Here, the authors describe a high-throughput screen to increase protein thermostability and identify thermostable variants from a broad range of proteins.
- Ignacio Asial
- , Yue Xiang Cheng
- & Tobias Cornvik
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Article |
Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster
Polycyclic tetramate macrolactams (PTMs) are natural products with important antifungal, antibiotic and antioxidant properties. Here, the authors apply a synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster from Streptomyces griseusand identify three putative PTMs.
- Yunzi Luo
- , Hua Huang
- & Huimin Zhao
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Article
| Open AccessBactericidal activity of black silicon
The topographical features of insect wings result in some interesting surface properties, including hydrophobicity and antibacterial activity. Here the authors identify the surface of black silicon as a mimic of dragonfly wings and show that it too possesses antibacterial activity.
- Elena P. Ivanova
- , Jafar Hasan
- & Russell J. Crawford
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Article
| Open AccessA closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice
Designer gene circuits allow the controlled expression of proteins in response to specific stimuli. Here, Rössger et al.use synthetic biology approaches to create a fatty-acid biosensor that controls the production of a satiety hormone and use it to control diet-induced obesity in mice.
- Katrin Rössger
- , Ghislaine Charpin-El-Hamri
- & Martin Fussenegger
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Article |
Biologically enhanced cathode design for improved capacity and cycle life for lithium-oxygen batteries
Lithium-oxygen batteries can deliver high-energy densities, but capacity, rate performance and cycle life are still critical issues. Oh et al.report biologically templated synthesis of manganese oxide nanowires, which exhibit excellent electrochemical performance and cost-efficiency.
- Dahyun Oh
- , Jifa Qi
- & Angela M. Belcher
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Article |
Probing single- to multi-cell level charge transport in Geobacter sulfurreducens DL-1
Microbial fuels cells present a way of generating electricity using the natural metabolism of microorganisms. Here the authors carry out single-cell current measurements ofGeobacter sulfurreducensDL-1 to determine the upper limits of microbial fuel cell performance.
- Xiaocheng Jiang
- , Jinsong Hu
- & Justin C. Biffinger
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Article |
Semiconductor-based DNA sequencing of histone modification states
Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.
- Christine S. Cheng
- , Kunal Rai
- & Ido Amit
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Article |
Programming adaptive control to evolve increased metabolite production
Cells can adapt rapidly to survive and efficiently exploit constantly changing environments by varying their mutation rate. Here the authors construct an in silicosystem to modulate mutation rate, and demonstrate that this method can be used in the laboratory to create specific phenotypes.
- Howard H. Chou
- & Jay D. Keasling
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Article |
Microbial biosynthesis of the anticoagulant precursor 4-hydroxycoumarin
4-hydroxycoumarin (4HC), a precursor for anticoagulant drugs such as warfarin, has a major role in the treatment of thromboembolic diseases. Here, the authors present an artificial biosynthetic pathway for 4HC production in E. coliand demonstrate its potential for large-scale microbial production.
- Yuheng Lin
- , Xiaolin Shen
- & Yajun Yan
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Article |
Tailoring the hydrophobicity of graphene for its use as nanopores for DNA translocation
Graphene nanopores hold great potential for single-molecule DNA screening; however, pore clogging due to hydrophobic interactions is a severe problem. Schneider et al. show that this can be prevented by non-covalently coating graphene with an ultrathin hydrophilic self-assembled monolayer.
- Grégory F. Schneider
- , Qiang Xu
- & Cees Dekker
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Article
| Open AccessZinc-finger nickase-mediated insertion of the lysostaphin gene into the beta-casein locus in cloned cows
Zinc-finger nickases are programmable nucleases that can be used to generate site-specific single-strand breaks in DNA. Liu et al. use this technology to insert an antimicrobial gene into the endogenous beta-casein locus in cloned cows, with the aim of providing protection against mastitis.
- Xu Liu
- , Yongsheng Wang
- & Yong Zhang
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Article
| Open AccessTargeted delivery of colloids by swimming bacteria
Transport of colloidal cargoes to target sites can be done by controlling active carriers, like self-propelled bacteria, under external stimuli. Koumakis et al.show that bacteria can autonomously achieve the same goal when moving over pre-designed asymmetric microstructures.
- N. Koumakis
- , A. Lepore
- & R. Di Leonardo
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Article |
Enhanced biofuel production through coupled acetic acid and xylose consumption by engineered yeast
Biofuel produced from renewable biomass is attractive, but inefficient conversion of cellulosic sugars and the toxicity of plant biomass hydrolysates hamper commercial production. Wei et al.use engineered yeast to address these problems simultaneously, converting both xylose and acetic acid into ethanol.
- Na Wei
- , Josh Quarterman
- & Yong-Su Jin
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Article
| Open AccessFunctional lacrimal gland regeneration by transplantation of a bioengineered organ germ
Lacrimal glands maintain a healthy corneal epithelium but are dysfunctional for example in dry-eye disease. Here, the authors transplant bioengineered lacrimal and harderian gland germs into mice, where they connect to the host duct and nervous system and restore lacrimal gland function.
- Masatoshi Hirayama
- , Miho Ogawa
- & Takashi Tsuji
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Article
| Open AccessFunctional salivary gland regeneration by transplantation of a bioengineered organ germ
Salivary gland dysfunction as a result of diseases or ageing reduces the quality of life and causes various oral health problems. Here the authors show that the salivary gland function of mice can be recovered by orthotopic transplantation of a bioengineered salivary gland germ.
- Miho Ogawa
- , Masamitsu Oshima
- & Takashi Tsuji
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Article |
Implementation of stable and complex biological systems through recombinase-assisted genome engineering
Genetic engineering of bacteria is an important tool in biotechnology and synthetic biology. Here, the authors describe a method for genomic integration of complex, multi-gene sequences into bacteria and use it to create a strain of E. colithat generates ethanol from brown macroalgae.
- Christine Nicole S. Santos
- , Drew D. Regitsky
- & Yasuo Yoshikuni
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Article |
Mutants of Cre recombinase with improved accuracy
Cre recombinase is widely used to precisely manipulate genes and chromosomes, but it often displays off-target activity. Here, the authors improve the accuracy of Cre-mediated recombination by introducing specific mutations in the enzyme’s dimerization surface.
- Nikolai Eroshenko
- & George M. Church
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Article
| Open AccessA nanopore machine promotes the vectorial transport of DNA across membranes
Transport of DNA molecules across lipid membranes requires protein conduits such as the nuclear pore complex. Franceschiniet al.engineer an artificial sequence-selective DNA transporter by attaching gating oligonucleotides to a bacterial nanopore.
- Lorenzo Franceschini
- , Misha Soskine
- & Giovanni Maglia
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Article |
Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres
Tissue engineering relies on the vascular compatibility of the synthesised constructs with target tissues. Here, the authors fabricate a prevascularised tissue construct of cell-laden hydrogel fibres as a framework that allows the formation of vascularised adipose and hepatic tissues.
- Meng Fatt Leong
- , Jerry K. C. Toh
- & Jackie Y. Ying
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Article |
Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells
Artificial heart tissue may find application in novel therapies of cardiac disease in the future. Here, Lu et al. take a step towards the creation of personalized heart tissue by repopulating decellularized mouse hearts with cells derived from human induced pluripotent stem cells.
- Tung-Ying Lu
- , Bo Lin
- & Lei Yang
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Article |
Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells
The potential tumorigenicity of human pluripotent stem cells (hPSCs) limits their application in cell therapies. Ben-David et al.identify the tight-junction protein Claudin-6 as a cell-surface marker of hPSCs, and demonstrate three Claudin-6-based strategies to remove tumorigenic hPSCs from mixed cell cultures.
- Uri Ben-David
- , Neta Nudel
- & Nissim Benvenisty
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