Biotechnology

  • Article
    | Open Access

    Brain organoids derived from human pluripotent stem cells can model human brain development and disease, though current culture systems fail to ensure reliable production of high-quality organoids. Here the authors combine human brain extracellular matrix and culture in a microfluidic device to promote structural and functional maturation of human brain organoids.

    • Ann-Na Cho
    • , Yoonhee Jin
    •  & Seung-Woo Cho
  • Article
    | Open Access

    Developing effective treatments for noncompressible hemorrhages remains a challenge. Here the authors engineer alkylated chitosan sponges with highly interconnective microchannels and demonstrate anti-infective activity, as well as higher pro-coagulant, hemostatic and wound healing capacities compared to clinically-used materials in rat and pig liver models.

    • Xinchen Du
    • , Le Wu
    •  & Meifeng Zhu
  • Article
    | Open Access

    Mutations in the LaminA gene are the second most common inherited cause of Dilated Cardiomyopathy, a major form of heart failure. Here the authors show that disruption of the nuclear protein SUN1 in cardiomyocytes, by AAV mediated transduction of a SUN1 inhibitor, significantly suppress cardiomyopathy progression, providing a potential therapeutic route to treat this disease.

    • Ruth Jinfen Chai
    • , Hendrikje Werner
    •  & Colin L. Stewart
  • Article
    | Open Access

    The authors have recently developed molecular force microscopy (MFM) which uses fluorescence polarisation to measure cell-surface receptor force orientation. Here they show that structured illumination microscopes, which inherently use fluorescence polarisation, can be used for MFM in a turn-key manner.

    • Aaron Blanchard
    • , J. Dale Combs
    •  & Khalid Salaita
  • Article
    | Open Access

    Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.

    • Yalda Afshar
    • , Jiantong Dong
    •  & Yazhen Zhu
  • Article
    | Open Access

    Many current immunoassays require multiple washing, incubation and optimization steps. Here the authors present Ratiometric Plug-and-Play Immunodiagnostics (RAPPID), a generic assay platform that uses ratiometric bioluminescent detection to allow sandwich immunoassays to be performed directly in solution.

    • Yan Ni
    • , Bas J. H. M. Rosier
    •  & Maarten Merkx
  • Article
    | Open Access

    Differentiation of hPSCs to cardiomyocytes suffers from high variability. Here the authors report a label-free live cell imaging platform based on autofluorescence imaging to enable the prediction of cardiomyocyte differentiation efficiency from hPSCs.

    • Tongcheng Qian
    • , Tiffany M. Heaster
    •  & Melissa C. Skala
  • Perspective
    | Open Access

    A key feature of living cells is the cell cycle. In this Perspective, the authors explore attempts to recreate this process and what is still required for an integrated synthetic cell cycle.

    • Lorenzo Olivi
    • , Mareike Berger
    •  & John van der Oost
  • Article
    | Open Access

    An efficient chassis for heterologous expression of biosynthetic gene clusters (BGCs) from Gram-negative bacteria is still unavailable. Here, the authors report rational construction of genome-reduced Burkholderials chassis to facilitate production of a class of new compounds by expressing BGC from Chitinimonas koreensis.

    • Jiaqi Liu
    • , Haibo Zhou
    •  & Xiaoying Bian
  • Article
    | Open Access

    Existing long-read de novo assembly methods can partially, but not completely, separate strains. Here, the authors develop Strainberry, a metagenome assembly bioinformatic pipeline that exclusively uses longread data to accurately separate and reconstruct strain genomes from single-sample low-complexity microbiomes.

    • Riccardo Vicedomini
    • , Christopher Quince
    •  & Rayan Chikhi
  • Article
    | Open Access

    Spatial analysis of RNAseq data is important. Here the authors report a method for transcriptome profiling combined with photo-isolation chemistry to allow determination of expression profiles specifically from photo-irradiated regions of interest which they use in mouse brains and embryonic tissues.

    • Mizuki Honda
    • , Shinya Oki
    •  & Yasuyuki Ohkawa
  • Article
    | Open Access

    DNA probes used in next generation sequencing (NGS) have variable hybridisation kinetics, resulting in non-uniform coverage. Here, the authors develop a deep learning model to predict NGS depth using DNA probe sequences and apply to human and non-human sequencing panels.

    • Jinny X. Zhang
    • , Boyan Yordanov
    •  & David Yu Zhang
  • Article
    | Open Access

    Esters can be used as fuels and specialty chemicals for food flavoring, cosmetic and pharmaceutical industries. Here, the authors systematically engineer clostridia, including discovery and deletion of prophages to increase strain stability, for the production of butyl acetate and butyl butyrate from corn stover at low cost.

    • Jun Feng
    • , Jie Zhang
    •  & Yi Wang
  • Article
    | Open Access

    Various GPCRs display constitutive ligand-independent activity, but it remains unclear whether ligand-dependent and -independent conformations differ. Here the authors demonstrate the recognition and blocking of G protein recruitment of either the ligand-bound active, or the constitutively active apo-conformation of the viral GPCR US28 by different nanobodies that target similar intracellular loops of the receptor.

    • Timo W. M. De Groof
    • , Nick D. Bergkamp
    •  & Martine J. Smit
  • Article
    | Open Access

    Self-powered implantable devices have the potential to extend device operation, though current energy harvesters are both insufficient and inconvenient. Here the authors report on a commercial coin battery-sized high-performance inertia-driven triboelectric nanogenerator based on body motion and gravity that can be used to charge a lithium-ion battery and integrated into a cardiac pacemaker.

    • Hanjun Ryu
    • , Hyun-moon Park
    •  & Sang-Woo Kim
  • Article
    | Open Access

    Current methods to estimate energy expenditure are either infeasible for everyday use or associated with significant errors. Here the authors present a Wearable System using inertial measurement units worn on the shank and thigh that estimates metabolic energy expenditure in real-time during common steady-state and time-varying activities.

    • Patrick Slade
    • , Mykel J. Kochenderfer
    •  & Steven H. Collins
  • Article
    | Open Access

    Finding durable, high-density media for data storage is necessary to support the ever-expanding generation of digital data. Here, the authors use peptide sequences to store digital data and retrieve them using tandem mass spectrometry, proving that peptides can be used as a storage medium.

    • Cheuk Chi A. Ng
    • , Wai Man Tam
    •  & Zhong-Ping Yao
  • Article
    | Open Access

    Single-cell RNA-seq reveals the cellular heterogeneity in development and disease. Here the authors present a single-nucleus RNA-seq2 that allows deep characterization of nuclei isolated from frozen archived tissues, apply it for transcriptional profiling of individual hepatocytes, and determine a functional crosstalk between liver zonation and ploidy.

    • M. L. Richter
    • , I. K. Deligiannis
    •  & C. P. Martinez-Jimenez
  • Article
    | Open Access

    Phospholipase A2 (PLA2) inhibitors have been shown to be able to treat acute pancreatitis, but are toxic with systemic application. Here the authors design a nanoparticle with macrophage membrane components to carry PLA2 inhibitor to macrophages and treat pancreatitis in mice, with no evidence of toxicity.

    • Qiangzhe Zhang
    • , Julia Zhou
    •  & Liangfang Zhang
  • Article
    | Open Access

    Shape memory scaffolds are needed for minimally invasive tissue repair and void filling. Here the authors report on the development of 4D printed polycarbonate-based scaffolds with surface degradation properties which fill voids without deforming tissue and allow for tissue ingrowth with reduced immune response.

    • Andrew C. Weems
    • , Maria C. Arno
    •  & Andrew P. Dove
  • Article
    | Open Access

    Limited understanding of the interactions between nanoparticle drug carriers and the blood-brain barrier underlies many translational failures in treatments of brain disorders. Here the authors use two-photon microscopy in mice to characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery from the blood to the brain in vivo.

    • Krzysztof Kucharz
    • , Kasper Kristensen
    •  & Martin Johannes Lauritzen
  • Article
    | Open Access

    Oncogenic RAS mutants remain difficult to target with small molecules. Here, the authors show that RAS-binding Affimer proteins inhibit RAS signaling while binding diverse regions on the RAS surface, suggesting the potential to use Affimers as tools to identify new binding pockets and pharmacophores.

    • Katarzyna Z. Haza
    • , Heather L. Martin
    •  & Darren C. Tomlinson
  • Article
    | Open Access

    Pyrrolysine (Pyl) exists in nature as the 22nd proteinogenic amino acid, but studies of Pyl have been hindered by the difficulty and inefficiency of both its chemical and biological syntheses. Here, the authors developed an improved PANCE approach to evolve the pylBCD pathway for increased production of Pyl proteins in E. coli.

    • Joanne M. L. Ho
    • , Corwin A. Miller
    •  & Matthew R. Bennett
  • Article
    | Open Access

    Current near-IR optogenetic systems to regulate transcription consist of a number of large protein components. Here the authors report a smaller single-component near-IR system, iLight, developed from a bacterial phytochrome that they use to control gene transcription in bacterial and mammalian cells.

    • Andrii A. Kaberniuk
    • , Mikhail Baloban
    •  & Vladislav V. Verkhusha
  • Article
    | Open Access

    The gene regulatory network controlling the bifurcation of common progenitors into the neural retina and retinal-pigmented epithelium programs remains poorly understood. Here the authors study transcriptome dynamics and chromatin accessibility during this process in zebrafish, revealing network redundancy, as well as context-dependent and sequential transcription factor activity.

    • Lorena Buono
    • , Jorge Corbacho
    •  & Juan-Ramón Martínez-Morales
  • Article
    | Open Access

    Here, the authors report de novo design, optimization and characterization of tRNAs that decode UGA stop codons in E. coli. The structure of the ribosome in a complex with the designed tRNA bound to a UGA stop codon suggests that distinct A-site ligands (tRNAs versus release factors) induce distinct conformation of the stop codon within the mRNA in the decoding center.

    • Suki Albers
    • , Bertrand Beckert
    •  & Zoya Ignatova
  • Article
    | Open Access

    Optimizing the concentration of different functional peptides on a surface can be a complex process. Here, the authors report on the use of a click immobilization strategy to create gradients of two different functional peptides on a surface to screen different density functions for rapid optimization.

    • Zhou Fang
    • , Junjian Chen
    •  & Chuanbin Mao
  • Article
    | Open Access

    Postsurgical adhesions are a problem during routine cardiothoracic procedures. Here, the authors report on a catechol functionalised hydrogel as an anti-adhesion material with improved retention on the heart which is biocompatible and biodegradable with minimal swelling, demonstrating application in vivo.

    • Masaki Fujita
    • , Gina M. Policastro
    •  & Karen L. Christman
  • Article
    | Open Access

    Base editing is one approach used to correct mutations causing cause Duchenne muscular dystrophy (DMD), but limitations are in the requirement for a specific PAM motif and the large size beyond the packaging capacity of adeno-associated virus (AAV). Here, the authors modify the NG-targeting adenine base editor to recognize a broader PAM, devise an intein split strategy to package the otherwise oversized adenine base editor into AAV, and show it efficiently restores dystrophin expression in muscle and heart when systemically injected in a mouse model of DMD

    • Li Xu
    • , Chen Zhang
    •  & Renzhi Han
  • Article
    | Open Access

    Single cell RNA-seq loses spatial information of gene expression in multicellular systems because tissue must be dissociated. Here, the authors show the spatial gene expression profiles can be both accurately and robustly reconstructed by a new computational method using a generative linear mapping, Perler.

    • Yasushi Okochi
    • , Shunta Sakaguchi
    •  & Honda Naoki
  • Article
    | Open Access

    Biomedical glues often face a challenge in providing strong adhesion and providing remodelling capabilities. Here the authors report on the development of a biocompatible and biodegradable protein-based coacervate adhesive and demonstrate application in haemostasis and wound healing using pig models.

    • Chao Ma
    • , Jing Sun
    •  & Andreas Herrmann
  • Article
    | Open Access

    Dysfunction of the lymphatic system leads to secondary lymphedema and results in degradation of quality of life. Here, the authors show that delivery of nucleoside-modified Vascular Endothelial Growth Factor C (VEGFC) mRNA, encapsulated in lipid nanoparticles, induces organ-specific lymphatic growth and reverses experimental lymphedema.

    • Dániel Szőke
    • , Gábor Kovács
    •  & Zoltán Jakus