Biotechnology articles within Nature Communications

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Artificially engineered tissues may be useful for regenerative therapies but their fabrication tends to be complicated. Stevens et al. present a technique for the precise organization of microstructurally complex tissues that works with a variety of cell types and does not require sophisticated equipment.

Guanine-rich DNA can form four-stranded structures called G-quadruplexes, which are thought to influence DNA replication, transcription and repair; their stability and prevalence in the genome is in need of further elucidation. Here the authors employ an antibody-based approach to sensitively map G-quadruplexes in the genome.

The identification of hosts of blood-sucking insects is important for studying ecological factors that affect pathogen distribution. Önder et al. report a proteomics-based methodology for the analysis of blood remnants in ticks that identifies the host species from which the tick has fed up to 6 months earlier.

Arginine-rich peptides act as delivery systems for the internalization of cargoes in cells. Here, the clustering of arginine units in a parallel array on a macrocyclic scaffold produces a vector with high efficiency in DNA delivery and transfection.

The complex shapes of biological tissues are often formed as a result of stress modulations. Wu et al.exploit such behaviour experimentally and theoretically to demonstrate a new mechanism of the formation of three-dimensional structures that is driven by engineered small-scale stresses within patterned hydrogel sheets.

Bacterial type III secretion systems (T3SS) improve the delivery of vaccine antigens and antigen-specific immune responses but require the use of live vaccines. Carleton et al. report the assembly of a functional T3SS in replication-incompetent bacterial minicells that can deliver vaccine antigens in vitro and in vivo.

A number of methylome sequencing technologies depend on affinity purification of methylated DNA. Zhang et al. demonstrate a click-chemistry-based protocol for covalently labelling 5-methylcytosine residues with biotin, providing enhanced sensitivity and specificity compared with antibody-based enrichment.

Primary sensory areas of newborn mammals typically display input-dependent plasticity. Thomson and colleagues use a sensory prosthetic device in rats to show that adult rats can discriminate different infrared light signals, when the signals are routed to somatosensory cortex by electrical microstimulation.

Gene circuits created by synthetic biologists working in one system may not be functional when transferred to a different organism. Using computational modelling to identify factors underlying such differences, the authors successfully adapt a yeast ‘linearizer’ circuit so that it functions in mammalian cells.

Genome-wide variation in the directed evolution of metabolite-overproducing microbes requires high-throughput screening platforms. Yang et al.show that synthetic RNA devices can sense target metabolites, enrich pathway optimisation, and expedite the evolution of metabolite-producing microbes.

Artificially engineered tissues may have many therapeutic applications but complex tissues are hard to create in vitro. Here, Okano and colleagues report the production of functional cardiac tissue sheets with perfusable blood vessels, which increase the thickness and survival of transplanted tissue.

3-hydroxy-γ-butyrolactone (3HBL) is a building block for many valuable drugs and is synthesized via a costly industrial process. Martin et al. engineer a novel biosynthetic pathway for the inexpensive production of 3HBL and other 3-hydroxyacids in E. coli.

Microbial fatty acid-derived fuels represent promising alternatives to the traditionally used fossil fuels. Koffas and colleagues report that E. colicentral metabolism can be modified to produce large quantities of fatty acids through a modular pathway engineering strategy.

Stem cells have raised hopes of developing regenerative therapies of renal disease. Here, Osafune et al.provide a protocol for the differentiation of induced human pluripotent stem cells into renal lineages with the capacity to form tubular renal structures in mice.

Genetic modification in insects mostly involves the use of fluorescent markers to identify successful transformation. Here Osanai-Futahashi et al.report a marker system based on changes in melanin pigmentation that allows the identification of genetically modified insects with the naked eye.

Microparticles are small vesicular structures that are shed from cellular plasma membranes. Tang and colleagues show that cells treated with chemotherapeutic drugs produce drug-containing microparticles, which can be used as anticancer agents in mice.

The ability of oleaginous fungi to produce lipids for biofuels remains untapped, in part due to a lack of genetic information required to engineer industrial strains. Zhuet al. present the genome of R. toruloides, and identify transcriptomic and proteomic changes associated with lipid production.

The lysosomal storage disease mucopolysaccharidosis I is treated with recombinant α-L-iduronidase but production of the enzyme is expensive. In this study, α-L-iduronidase is compartmentalized within the endosperm of maize via a unique mRNA strategy yielding the active, correctly glycosylated protein.

Calcium-sensing fluorescent proteins such as TN-XXL are valuable tools for studying cellular function but, when expressed in mice, may affect animal physiology and behaviour. The authors of this paper create transgenic mice expressing TN-XXL and show that long-term expression of TN-XXL is tolerated well.