Biotechnology

  • Article
    | Open Access

    Wheat production is threatened by wheat yellow mosaic virus (WYMV). Here, via genome-wide association study, the authors report that a putative methyltransferase B positively regulates WYMV infection through enhancing viral genomic RNA stability by N6-methyladenosine RNA modification.

    • Tianye Zhang
    • , Chaonan Shi
    •  & Jian Yang
  • Article
    | Open Access

    Chimeric antigen receptors (CAR) are a promising option for cell-based immunotherapy for cancer and other immune diseases. Here the authors develop speedingCARs, an integrated CAR design and screening platform based on modular signaling domain shuffling and single cell transcriptomic analyses, and test its potential for identifying and validating novel CAR designs.

    • Rocío Castellanos-Rueda
    • , Raphaël B. Di Roberto
    •  & Sai T. Reddy
  • Article
    | Open Access

    Shoot branching is critical in determining soybean yield. Here, the authors report natural variation of Dt2 in controlling soybean branching number and the interaction of Dt2 with GmAgl22 and GmSoc1a to activate transcription of GmAp1a and GmAp1d.

    • Qianjin Liang
    • , Liyu Chen
    •  & Zhixi Tian
  • Article
    | Open Access

    Achieving spatial control of gene expression is important. Here the authors report an optimised photoactivatable Cre recombinase system, doxycycline- and light-inducible Cre recombinase (DiLiCre), and generate a DiLiCre mouse line which they use for mutagenesis in vivo and positional cell-tracing.

    • Miguel Vizoso
    • , Colin E. J. Pritchard
    •  & Jacco van Rheenen
  • Article
    | Open Access

    Biosynthesis of the flavonoid naringenin in plants and bacteria is commonly catalysed by a type III polyketide synthase (PKS) using one p-coumaroyl-CoA and three malonyl-CoA molecules as substrates. Here, the authors report a fungal non-ribosomal peptide synthetase PKS hybrid FnsA catalysing the formation of naringenin.

    • Hongjiao Zhang
    • , Zixin Li
    •  & Wen-Bing Yin
  • Article
    | Open Access

    Here, the authors construct 102 complete metagenome-assembled genomes (cMAGs) from Pacific Biosciences (PacBio) high-accuracy long-read (HiFi) metagenomic sequencing, showing as high nucleotide accuracy as reference genomes and revealing that regions hard to assemble by short-read sequencing comprise mostly of genomic islands and rRNAs.

    • Chan Yeong Kim
    • , Junyeong Ma
    •  & Insuk Lee
  • Article
    | Open Access

    The induction of long-term systemic immunosurveillance can protect against post-surgery tumor recurrence. Here the authors describe the design of optogenetic-controlled cytokine secreting (IFN-β, TNF-α, and IL-12) engineered mesenchymal stem cells loaded into a hydrogel scaffold, eliciting long-term immune memory and preventing post-operative recurrence in preclinical cancer models.

    • Yuanhuan Yu
    • , Xin Wu
    •  & Haifeng Ye
  • Article
    | Open Access

    β-TrCP plays an important role in diverse cellular processes such as the cell cycle and inflammation. Here the authors develop a biosensor for β-TrCP activity and use it to investigate β-TrCP dynamics during the cell cycle, and to screen a small-molecule library for β-TrCP activators and inhibitors.

    • Debasish Paul
    • , Stephen C. Kales
    •  & Steven D. Cappell
  • Article
    | Open Access

    Transgenic modification of silkworms has the potential to engineer new silks with a wider range of properties. Here, the authors engineered the expression of the outer layer sericin SER3 in the inner fibroin layer generating a new silk with higher production efficiency and resistance to alkaline conditions.

    • Xuedong Chen
    • , Yongfeng Wang
    •  & Shiqing Xu
  • Article
    | Open Access

    It is important to understand the enzymatic degradation of wood biomass by lytic polysaccharide monooxygenase, however, disagreements about the co-substrate exist. Here, the authors use piezo-controlled hydrogen peroxide micro-sensors to demonstrate that even low levels of hydrogen peroxide support the enzymatic degradation of wood cell walls.

    • Hucheng Chang
    • , Neus Gacias Amengual
    •  & Roland Ludwig
  • Article
    | Open Access

    Cost-effective methods for long-term storage of DNA are desired. Here the authors present a method for in situ cryosilicification of whole blood cells, allowing long-term and room temperature preservation of genomic information for only approximately $0.5 per sample.

    • Liang Zhou
    • , Qi Lei
    •  & Wei Zhu
  • Article
    | Open Access

    Bioactive peptides regulate many physiological functions but progress in discovering them has been slow. Here, the authors use a machine learning framework to predict mammalian peptide candidates from the global and local structure of large-scale tissue-specific mass spectrometry data.

    • Christian T. Madsen
    • , Jan C. Refsgaard
    •  & Ulrik de Lichtenberg
  • Perspective
    | Open Access

    Long-duration human space travel creates challenges for maintaining healthy diets. Here the authors discuss using synthetic biology approaches to modify yeast into an optimal, and enjoyable, food production platform.

    • Briardo Llorente
    • , Thomas C. Williams
    •  & Ian T. Paulsen
  • Article
    | Open Access

    G protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. Here the authors, using heterologous GPCR expression and endogenous ligand production, enable synthetic mating in haploid yeast, and GPCR-mediated biosensing in diploid probiotic yeast.

    • Emil D. Jensen
    • , Marcus Deichmann
    •  & Michael K. Jensen
  • Article
    | Open Access

    Surface modification of nanoparticles by cell membrane (CM) coating to improve their bio-interface properties often results in partial coating. Here the authors show that partial coating is an intermediate state due to the absorption of CM fragments or vesicles and can be resolved by increasing CM fluidity with external phospholipids.

    • Lizhi Liu
    • , Dingyi Pan
    •  & Vesa-Pekka Lehto
  • Article
    | Open Access

    A pediatric RSV vaccine is an unmet medical need, even after >50 years of effort. Here, the authors show that a chimpanzee adenovirus based RSV vaccine candidate protects calves from disease upon RSV infection, regardless of the time after vaccination (1 or 4 months) or the presence of maternal antibodies.

    • Rineke de Jong
    • , Norbert Stockhofe-Zurwieden
    •  & Ann-Muriel Steff
  • Article
    | Open Access

    Disrupting the association between the Immunoglobulin G constant fragment (Fc) and the neonatal Fc receptor (FcRn) by engineered antibodies is a promising strategy to reduce autoantibody levels in autoimmune diseases. Here authors show that the variable fragment (Fab) of immunoglobulins could disturb the Fc-FcRn interaction, therefore the therapeutic effect of Fc-only fragments might surpass that of Fc-engineered antibodies with enhanced binding to FcRn.

    • Maximilian Brinkhaus
    • , Erwin Pannecoucke
    •  & Gestur Vidarsson
  • Article
    | Open Access

    Adoptive cell therapies (ACT) hold promise for cancer immunotherapy, but optimization is still an ongoing process. Here the authors report CD4-targeted, nanoparticle-based artificial antigen-presenting cells that expand CD4+ T cells capable of lysing tumor cell lysis in vitro, and CD8+ T cells showing antitumor activity in a mouse melanoma model.

    • Ariel Isser
    • , Aliyah B. Silver
    •  & Jonathan P. Schneck
  • Article
    | Open Access

    Transplanting encapsulated insulin-producing cells may achieve a functional cure for type 1 diabetes, but efficacy is constrained by mass transfer limits. Here, the authors report a dynamic computational platform to investigate the therapeutic potency of such programmable bioartificial pancreas devices.

    • Alexander U. Ernst
    • , Long-Hai Wang
    •  & Minglin Ma
  • Article
    | Open Access

    Lower concentrations of toxic cryoprotective agents require rapid and scalable rewarming techniques. Here, the authors report on a joule heating–based platform where samples are rapidly rewarmed by contact with a voltage pulsed electrical conductor and demonstrate the preservation of Drosophila embryos and rat kidney slices.

    • Li Zhan
    • , Zonghu Han
    •  & John C. Bischof
  • Article
    | Open Access

    Targeted nanoparticle delivery to sites of interest is important for targeted therapeutics. Here, the authors improve the targeting efficiency of antibodies on nanoparticles using a monobody adapter to correctly orientate the antibody to preserve targeting function and demonstrate application in targeting the vascular endothelium of human kidneys.

    • C. Albert
    • , L. Bracaglia
    •  & G. T. Tietjen
  • Article
    | Open Access

    Bacterial cells utilize cholesterol-enhanced pore formation to specifically target eukaryotic cells. Here, the authors present a class of bio-inspired, cholesterol-enhanced nanopores which display anticancer activities in vitro.

    • Jie Shen
    • , Yongting Gu
    •  & Huaqiang Zeng
  • Article
    | Open Access

    Here, the authors present a rare example of sympatric homoploid hybrid speciation, without ploidy changes, in the Midas cichlid fishes from Nicaragua. Midas cichlid hybrids occupy a different ecological niche, likely facilitated by body shape adaptations.

    • Melisa Olave
    • , Alexander Nater
    •  & Axel Meyer
  • Article
    | Open Access

    Antimicrobial peptides (AMPs) are promising next-generation antibiotics, but are difficult to produce due to the toxicity to bacterial hosts. Here, the authors report the utilization of transplastomic tobacco plants for AMPs production without cytotoxic effects via inducible expression systems and fusions to cleavable carrier protein.

    • Matthijs P. Hoelscher
    • , Joachim Forner
    •  & Ralph Bock
  • Article
    | Open Access

    Applications of the SCRaMbLE process are hindered due to the lack of facile and tight regulation and limited understanding of key factors that may affect the rearrangement outcomes. Here the authors present an approach to precisely regulate SCRaMbLE recombination in a dose-dependent manner using genetic code expansion technology with low basal activity.

    • Huiming Zhang
    • , Xian Fu
    •  & Yue Shen
  • Article
    | Open Access

    The immunoglobulin domain framework of antibodies has been a long standing design challenge. Here, the authors describe design rules for tailoring these domains and show they can be accurately designed, de novo, with high stability and the ability to scaffold functional loops.

    • Tamuka M. Chidyausiku
    • , Soraia R. Mendes
    •  & Enrique Marcos
  • Article
    | Open Access

    COVID-19 can be treated with monoclonal antibodies against SARS-CoV-2, but emerging new variants might show resistance towards existing therapy. Here authors show that anti-SARS-CoV-2 spike human single-chain antibody fragments could gain neutralizing activity against variants of concern upon engineering into a human bispecific antibody.

    • Matthew R. Chang
    • , Luke Tomasovic
    •  & Wayne A. Marasco
  • Article
    | Open Access

    Precise and reliable gene delivery remains technically challenging. Here, the authors show that rationally designed frameshifting splicing can be used to express genes only in targeted cell types, with the potential to enhance the specificity AAV gene delivery.

    • Jonathan P. Ling
    • , Alexei M. Bygrave
    •  & Seth Blackshaw
  • Article
    | Open Access

    Management of ulcerative colitis can require a combination of treatments targeting different pathways. Here the authors design a therapy for ulcerative colitis based on a multitargeted genetic circuit to simultaneously target TNF-α, B7-1 and integrin α4, and show the therapy is effective in male mice with induced or spontaneous genetic colitis.

    • Xinyan Zhou
    • , Mengchao Yu
    •  & Xi Chen
  • Article
    | Open Access

    Hydrogenation is a treatment for chronic inflammation caused by high glucose levels in diabetic ulcers, However, current therapies have limitations. Here, the authors report on the creation of a visible light photocatalytic agent which depletes glucose in the wound and generates hydrogen to aid in diabetic wound healing.

    • Shengqiang Chen
    • , Yanxia Zhu
    •  & Qianjun He
  • Article
    | Open Access

    “Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. Here the authors show that PopZ condensate dynamics support cell division and using PopZ modular architecture, the tunable PopTag platform was developed to enable designer condensates.”

    • Keren Lasker
    • , Steven Boeynaems
    •  & Lucy Shapiro
  • Article
    | Open Access

    Marine ecosystems are dominated by microbial communities. Inspired by the photoelectric conversion feature of the marine ecosystems, the authors design a four-species microbial community to mimic primary producer, primary degrader, and ultimate consumers, and show its ability to convert light into electricity for over one month.

    • Huawei Zhu
    • , Liru Xu
    •  & Yin Li
  • Article
    | Open Access

    Fluorescent tracers facilitate the identification and subsequent collection of tumour draining lymph node biopsies, enabling important clinical assessment. Here, the authors present a molecular gold nanocluster NIR-II fluorescent imaging probe and demonstrate its utility to visualise draining lymph nodes in breast and colon cancer mouse models.

    • Ani Baghdasaryan
    • , Feifei Wang
    •  & Hongjie Dai
  • Article
    | Open Access

    Computational properties of neuronal networks have been applied to computing systems using simplified models comprising repeated connected nodes. Here the authors create layered assemblies of genetically encoded devices that perform non-binary logic computation and signal processing using combinatorial promoters and feedback regulation.

    • Luna Rizik
    • , Loai Danial
    •  & Ramez Daniel
  • Article
    | Open Access

    Managing herbicide resistance problem needs the identification of new herbicidal modes of action. Here, the authors solve the crystal structures of Arabidopsis HMGR and show HMGR as a potential new herbicide target by identifying plant-specific HMGR inhibitors and engineering tolerant trait in Arabidopsis.

    • Joel Haywood
    • , Karen J. Breese
    •  & Joshua S. Mylne
  • Article
    | Open Access

    Engineered living materials (ELMs) embed living cells in a biopolymer matrix to create novel materials with tailored functions. In this work, the authors engineered bacteria to grow novel macroscopic materials that can be reshaped, functionalized, and used to filter contaminated water while also showing that the stiffness of these materials can be tuned through genetic changes.

    • Sara Molinari
    • , Robert F. Tesoriero Jr.
    •  & Caroline M. Ajo-Franklin
  • Article
    | Open Access

    Assembly artificial pathway in design connecting media can increase biosynthetic efficiency, but the choice of connecting media is limited. Here, the authors develop a new protein assembly strategy using a pool of docking peptides from polyketide synthase and show its application in astaxanthin biosynthesis in E. coli.

    • Xixi Sun
    • , Yujie Yuan
    •  & Tian Ma
  • Article
    | Open Access

    Microbial production of cannabinoids promises a cheaper and more sustainable route to these important therapeutic molecules, but strain improvement and screening is challenging. Here, the authors develop a yeast-based Δ9-tetrahydrocannabinol (THC) biosensor for screening microbial mutant libraries.

    • William M. Shaw
    • , Yunfeng Zhang
    •  & Tom Ellis