Featured
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Article
| Open AccessReprogramming bacterial protein organelles as a nanoreactor for hydrogen production
The extreme oxygen sensitive character of hydrogenases is a longstanding issue for hydrogen production in bacteria. Here, the authors build carboxysome shells in E. coli and incorporate catalytically active hydrogenases and functional partners within the empty shell for the production of hydrogen.
- Tianpei Li
- , Qiuyao Jiang
- & Lu-Ning Liu
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Article
| Open AccessNatural variations of SLG1 confer high-temperature tolerance in indica rice
Understanding the mechanism of high-temperature tolerance will help to breed crops adaptive to warming climate. Here, the authors show SLG1, a cytosolic tRNA 2-thiolation protein 2 encoding gene, is differentiated between the two Asian cultivated rice subspecies and confers high temperature tolerance of indica rice.
- Yufang Xu
- , Li Zhang
- & Shanguo Yao
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Article
| Open AccessGenome biology of the paleotetraploid perennial biomass crop Miscanthus
The perennial grass Miscanthus is a promising biomass crop. Here, via genomics and transcriptomics, the authors reveal its allotetraploid origin, characterize gene expression associated with rhizome development and nutrient recycling, and describe the hybrid origin of the triploid M. x giganteus.
- Therese Mitros
- , Adam M. Session
- & Daniel S. Rokhsar
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Article
| Open AccessIdentification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants
Adeno-associated virus is the basis of many gene therapies and gene transfer vectors. Here the authors report a pipeline to enable side-by-side comparison of pre-selected capsids in a high throughput manner.
- Jonas Weinmann
- , Sabrina Weis
- & Dirk Grimm
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Article
| Open AccessNuclear gene proximity and protein interactions shape transcript covariations in mammalian single cells
Gene expression covariation can be studied by single-cell RNA sequencing. Here the authors analyze intrinsically covarying gene pairs by eliminating the confounding effects in single-cell experiments and observe covariation of proximal genes and miRNA-induced covariation of target mRNAs.
- Marcel Tarbier
- , Sebastian D. Mackowiak
- & Marc R. Friedländer
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Article
| Open AccessGenetically engineered magnetic nanocages for cancer magneto-catalytic theranostics
The clinical application of magnetic hyperthermia therapy (MHT) is limited by the poor magnetic-to-thermal conversion efficiency of MHT agents. Here, the authors develop encapsulin-produced magnetic iron oxide nanocomposites (eMIONs) with excellent magnetic-heat capability and catalysis-triggered tumor suppression ability to overcome the critical issues of MHT.
- Yang Zhang
- , Xiaoyong Wang
- & Gang Liu
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Article
| Open AccessModeling early stage atherosclerosis in a primary human vascular microphysiological system
Human microphysiological systems (MPS) have some advantages over animal models to study the mechanisms of disease. Here the authors use a tissue-engineered blood vessel MPS to create a model of early stage atherosclerosis and assess the effect of several drugs.
- Xu Zhang
- , Muath Bishawi
- & George A. Truskey
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Article
| Open AccessMethanol-dependent Escherichia coli strains with a complete ribulose monophosphate cycle
The engineering of methanol-dependent growth in Escherichia coli is challenging. Here, the authors predict and experimentally validate methanol-dependent strains with a complete RuMP cycle and high potential for the development of a methylotrophic platform organism.
- Philipp Keller
- , Elad Noor
- & Julia A. Vorholt
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Article
| Open AccessGenome-scale metabolic rewiring improves titers rates and yields of the non-native product indigoidine at scale
The trade-off between growth and production affects the application of engineered microbes. Here, the authors take the minimal cut set approach to predict metabolic reactions for elimination to couple metabolite production strongly with growth and achieve high production of indigoidine in Pseudomonas putida.
- Deepanwita Banerjee
- , Thomas Eng
- & Aindrila Mukhopadhyay
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Article
| Open AccessPrime editing for functional repair in patient-derived disease models
Prime editing uses Cas9 nickase fused to a reverse transcriptase to edit genetic information. Here, the authors prime edit primary adult stem cells in 3D organoid cultures to show functional correction of pathogenic mutations without genome-wide off-target effects.
- Imre F. Schene
- , Indi P. Joore
- & Sabine A. Fuchs
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Article
| Open AccessCarotenoids modulate kernel texture in maize by influencing amyloplast envelope integrity
Very little is known about how vitreous endosperm in the mature maize kernel is created. Here, via map-based cloning, the authors find that mutation of a β-carotene hydroxylase 3 encoding gene Ven1 affects carotenoids and lipids composition, which consequently influences amyloplast envelope integrity.
- Haihai Wang
- , Yongcai Huang
- & Yongrui Wu
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Article
| Open AccessMSH1-induced heritable enhanced growth vigor through grafting is associated with the RdDM pathway in plants
The meiotic transmissibility and progeny phenotypic influence of graft-mediated epigenetic changes remain unclear. Here, the authors use the msh1 mutant in the rootstock to trigger heritable enhanced growth vigor in Arabidopsis and tomato, and show it is associated with the RNA-directed DNA methylation pathway.
- Hardik Kundariya
- , Xiaodong Yang
- & Sally A. Mackenzie
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Article
| Open AccessLow cost DNA data storage using photolithographic synthesis and advanced information reconstruction and error correction
The current bottleneck for DNA data storage systems is the cost and speed of synthesis. Here, the authors use inexpensive, massively parallel light-directed synthesis and correct for a high error rate with a pipeline of encoding and reconstruction algorithms.
- Philipp L. Antkowiak
- , Jory Lietard
- & Robert N. Grass
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Article
| Open AccessVestigial-like 1 is a shared targetable cancer-placenta antigen expressed by pancreatic and basal-like breast cancers
Cytotoxic T lymphocyte (CTL)-based immunotherapies can induce tumor regressions by targeting HLA class I-bound tumor-associated peptides. Here, the authors identified a peptide derived from Vestigial-like 1 (VGLL1) as a shared, potentially therapeutic CTL target expressed by multiple cancer types.
- Sherille D. Bradley
- , Amjad H. Talukder
- & Gregory Lizée
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Article
| Open Access5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation
The relative enrichment of cancer stem cells after treatment results in tumour recurrence. Here, the authors show a mechanism where p53 induces WNT3, which increases the number of colorectal cancer stem cells following treatment of 5-fluorouracil.
- Yong-Hee Cho
- , Eun Ji Ro
- & Kang-Yell Choi
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Article
| Open AccessDirect reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells
The conditions to induce human hepatic progenitor cells from other cell types are unclear. Here, the authors reprogram human endothelial cells to hepatic progenitor cells by expressing FOXA3, HNF1A and HNF6, capable of giving rise to hepatocytes and cholangiocytes that reconstitute damaged liver tissues on transplantation.
- Hiroki Inada
- , Miyako Udono
- & Atsushi Suzuki
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Article
| Open AccessChromosome-level genome assembly of a parent species of widely cultivated azaleas
Azaleas are one of the most diverse ornamental plants and have cultural and economic importance. Here, the authors report a chromosome-scale genome assembly for the primary ancestor of the azalea cultivar Rhododendro simsi and identify transcription factors that may function in flower coloration at different stages.
- Fu-Sheng Yang
- , Shuai Nie
- & Jian-Feng Mao
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Article
| Open AccessAutomated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids
The use of organoids in personalized medicine is promising but high throughput platforms are needed. Here the authors develop an automated, high-throughput, microfluidic 3D organoid culture system that allows combinatorial and dynamic drug treatments and real-time analysis of organoids.
- Brooke Schuster
- , Michael Junkin
- & Savaş Tay
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Comment
| Open AccessThe human microbiome in the 21st century
The human body supports a thriving diversity of microbes which comprise a dynamic, ancillary, functional system that synergistically develops in lock-step with physiological development of its host. The human microbiome field has transitioned from cataloging this rich diversity to dissecting molecular mechanisms by which microbiomes influence human health. Early life microbiome development trains immune function. Thus, vertically, horizontally, and environmentally acquired microbes and their metabolites have the potential to shape developmental trajectories with life-long implications for health.
- Elze Rackaityte
- & Susan V. Lynch
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Article
| Open AccessPhoton-directed multiplexed enzymatic DNA synthesis for molecular digital data storage
Writing data in DNA is still a bottleneck due to the reliance on chemical synthesis methods. Here the authors report multiplexed enzymatic DNA synthesis using maskless photolithography.
- Howon Lee
- , Daniel J. Wiegand
- & George M. Church
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Article
| Open AccessGPAHex-A synthetic biology platform for Type IV–V glycopeptide antibiotic production and discovery
Expansion of the chemical diversity of glycopeptide antibiotics (GPAs) to deal with the emergence and spread of GPA resistance is challenging. Here, the authors report a GPA synthetic biology platform in Streptomyces coelicolor for Type IV–V glycopeptide antibiotic production and discovery.
- Min Xu
- , Wenliang Wang
- & Gerard D. Wright
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Article
| Open AccessDetection of haplotype-dependent allele-specific DNA methylation in WGBS data
Allele-specific measurements can reveal differences in DNA methylation between homologous alleles associated with changes in genetic sequence. Here, the authors develop a method for detecting allele specific methylation events within haplotypes of linked SNPs, compare it with existing methods, and show it identifies haplotypes for which the genetic variant carries significant information about the methylation state of the allele of origin.
- J. Abante
- , Y. Fang
- & J. Goutsias
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Article
| Open AccessStandardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies
Distributed multi-omic digitization of clinical specimen across multiple sites is a prerequisite for turning molecular precision medicine into reality. Here, the authors show that coordinated proteotype data acquisition is feasible using standardized MS data acquisition and analysis strategies.
- Yue Xuan
- , Nicholas W. Bateman
- & Thomas P. Conrads
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Perspective
| Open AccessMultiplying the efficiency and impact of biofortification through metabolic engineering
Biofortification is an effective means to reduce micronutrient malnutrition. Here, the authors review recent advances in biofortification and propose stacking multiple micronutrient traits into high-yielding varieties through the combination of conventional breeding and genetic engineering approaches.
- Dominique Van Der Straeten
- , Navreet K. Bhullar
- & Howarth Bouis
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Article
| Open AccessEngineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins
ADP-ribose binding macro domains facilitate the enrichment and detection of cellular ADP-ribosylation. Here, the authors generate an engineered macro domain with increased ADP-ribose affinity, improving the identification of ADP-ribosylated proteins by proteomics, western blot and immunofluorescence.
- Kathrin Nowak
- , Florian Rosenthal
- & Michael O. Hottiger
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Comment
| Open AccessThe second decade of synthetic biology: 2010–2020
Synthetic biology is among the most hyped research topics this century, and in 2010 it entered its teenage years. But rather than these being a problematic time, we’ve seen synthetic biology blossom and deliver many new technologies and landmark achievements.
- Fankang Meng
- & Tom Ellis
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Review Article
| Open AccessACE2 mouse models: a toolbox for cardiovascular and pulmonary research
Angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme previously shown to mediate SARS-CoV, and now SARS-CoV-2, entry into host cells. Here the authors review existing mouse ACE2 models expressing humanized, transgenic, knockout, knockin, conditional and reporter alleles to provide a toolbox for COVID-19 research.
- Hongpeng Jia
- , Xinping Yue
- & Eric Lazartigues
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Article
| Open AccessFermentative production of Vitamin E tocotrienols in Saccharomyces cerevisiae under cold-shock-triggered temperature control
Tocotrienols are valuable supplementations to α-tocopherol-dominated Vitamin E products. Here, the authors engineer baker’s yeast by combining the heterologous genes from photosynthetic organisms with the endogenous pathway for the production of tocotrienols under cold-shock-triggered temperature control.
- Bin Shen
- , Pingping Zhou
- & Hongwei Yu
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Article
| Open AccessDeep transfer learning for reducing health care disparities arising from biomedical data inequality
Developing machine learning models that work equally well for all ethnic groups is of crucial importance to health disparity prevention and reduction. Here, using an extensive set of machine learning experiments on cancer omics data, the authors find that transfer learning can improve model performance for data-disadvantaged ethnic groups.
- Yan Gao
- & Yan Cui
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Article
| Open AccessReconstructing the maize leaf regulatory network using ChIP-seq data of 104 transcription factors
Transcriptional factors (TFs) bind in a combinatorial fashion to specify the on-and-off states of genes in a complex and redundant regulatory network. Here, the authors construct the transcription regulatory network in maize leaf using 104 TFs ChIP-seq data and train machine learning models to predict TF binding and colocalization.
- Xiaoyu Tu
- , María Katherine Mejía-Guerra
- & Silin Zhong
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Article
| Open AccessResonance energy transfer sensitises and monitors in situ switching of LOV2-based optogenetic actuators
Cellular optogenetics applications are limited by difficulties in quantification and blue light toxicity. Here the authors design LOV2-based switches that use resonance energy transfer to overcome these concerns.
- Li-Li Li
- , Florence M. Klein
- & Michael J. Courtney
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Article
| Open AccessA versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands
Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a family of immunomodulatory receptors expressed on cells of the hematopoietic lineage. Here the authors demonstrate an approach for the identification of the glycan ligands of Siglecs, which is also applicable to other families of glycan-binding proteins.
- Emily Rodrigues
- , Jaesoo Jung
- & Matthew S. Macauley
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Article
| Open AccessTitrating bacterial growth and chemical biosynthesis for efficient N-acetylglucosamine and N-acetylneuraminic acid bioproduction
An imbalance between cell growth and bioproduction of engineered microbes often reduces production efficiency. Here, the authors report genetic code expansion-based cell growth and biosynthesis balance engineering to achieve high levels production of N-acetylglucosamine in E. coli and N-acetylneuraminic acid in B. subtilis.
- Rongzhen Tian
- , Yanfeng Liu
- & Jian Chen
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Article
| Open AccessOrigin and adaptation to high altitude of Tibetan semi-wild wheat
Mechanism of high altitude adaptation of wheat remains unknown. Here, the authors assemble the draft genome of a Tibetan semi-wild wheat accession and resequence 245 wheat accessions to reveal that Tibetan semi-wild wheat has been de-domesticated from local landraces to adapt to high altitude.
- Weilong Guo
- , Mingming Xin
- & Qixin Sun
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Article
| Open AccessIn vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells
Fusion oncogenes (FO) are common in cancers, but specific targeting of these chimeric genes are challenging. Here the authors report a CRISPR/Cas9 strategy that targets two intronic regions to disrupt the FOs in cancer cells and show that this approach reduces tumour growth and prolongs survival in animal models of cancer.
- M. Martinez-Lage
- , R. Torres-Ruiz
- & S. Rodriguez-Perales
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Article
| Open AccessA fluoride-responsive genetic circuit enables in vivo biofluorination in engineered Pseudomonas putida
Addition of fluorine to organic structures is a unique strategy for tuning molecular properties, but approaches to integrate fluorometabolites into the biochemistry of living cells are scarce. Here, the authors develop a fluoride-responsive genetic circuit to enable in vivo biofluorination in engineered Pseudomonas putida.
- Patricia Calero
- , Daniel C. Volke
- & Pablo I. Nikel
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Article
| Open AccessA deep learning approach to programmable RNA switches
RNA can be used as a programmable tool for detection of biological analytes. Here the authors use deep neural networks to predict toehold switch functionality in synthetic biology applications.
- Nicolaas M. Angenent-Mari
- , Alexander S. Garruss
- & James J. Collins
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Article
| Open AccessIdentification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis
The pathophysiology of epilepsy is unclear. Here, the authors present single-nuclei transcriptomic profiling of human temporal lobe epilepsy from patients. They identified epilepsy-associated neuronal subtypes, and a panel of dysregulated genes, predicting neuronal circuits contributing to epilepsy.
- Ulrich Pfisterer
- , Viktor Petukhov
- & Konstantin Khodosevich
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Article
| Open AccessProtease circuits for processing biological information
In contrast to genetic circuits, here the authors develop protein biocircuits based on proteases. They show these activity-based circuits can execute Boolean logic for programmable drug delivery and perform fuzzy logic to solve a mathematical oracle problem, Learning Parity with Noise.
- Brandon Alexander Holt
- & Gabriel A. Kwong
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Article
| Open AccessMetastable hybridization-based DNA information storage to allow rapid and permanent erasure
The chemical stability of DNA makes complete erasure of DNA-encoded data difficult. Here the authors mix true and false messages, differentiated by whether a truth marker oligo is bound to it, and show that brief exposure to elevated temperatures randomizes the binding of truth markers preventing data recovery.
- Jangwon Kim
- , Jin H. Bae
- & David Yu Zhang
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Article
| Open AccessIn situ reprogramming of gut bacteria by oral delivery
It is difficult to precisely target bacterial populations in the mammalian gut. Here the authors use encapsulated phages to deliver dCas9 to E. coli in the mouse gut to modulate RFP expression.
- Bryan B. Hsu
- , Isaac N. Plant
- & Pamela A. Silver
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Article
| Open AccessTailoring poplar lignin without yield penalty by combining a null and haploinsufficient CINNAMOYL-CoA REDUCTASE2 allele
Plants with reduced amounts of lignin typically suffer from dwarfed growth, which offsets their gain in fermentable sugar yield. Here, the authors show that genome-edited poplar lines with a null and a haploinsufficient allele of CINNAMOYL-COA REDUCTASE2 (CCR2) can be obtained that have a reduced lignin level and normal growth.
- Barbara De Meester
- , Barbara Madariaga Calderón
- & Wout Boerjan
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Article
| Open AccessFormat chain exchange (FORCE) for high-throughput generation of bispecific antibodies in combinatorial binder-format matrices
Bispecific antibodies have been generated in many different formats and it is becoming clear that rational design alone cannot create optimal functionalities. Here the authors introduce the high throughput methodology, Format Chain Exchange (FORCE), to enable combinatorial generation of bispecific antibodies.
- Stefan Dengl
- , Klaus Mayer
- & Ulrich Brinkmann
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Article
| Open AccessEnhancement of trans-cleavage activity of Cas12a with engineered crRNA enables amplified nucleic acid detection
CRISPR-Cas12a based detection systems can be sensitive down to the picomolar range. Here the authors modify the 3′- and 5′-ends of the crRNA and show this enhances trans-cleavage for improved sensitivity.
- Long T. Nguyen
- , Brianna M. Smith
- & Piyush K. Jain
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Article
| Open AccessHomopolymer self-assembly of poly(propylene sulfone) hydrogels via dynamic noncovalent sulfone–sulfone bonding
Natural biomolecules such as peptides and DNA can dynamically self-organize into diverse hierarchical structures. Here the authors report experiments and simulations on the dynamic network self-assembly and subsequent collapse of the synthetic homopolymer poly(propylene sulfone).
- Fanfan Du
- , Baofu Qiao
- & Evan Alexander Scott
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Article
| Open AccessViral gene drive in herpesviruses
Current gene drive strategies are restricted to sexually reproducing species. Here the authors develop a gene drive in herpesviruses that allows the spread of an engineered trait through a viral population.
- Marius Walter
- & Eric Verdin
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Article
| Open AccessA machine learning Automated Recommendation Tool for synthetic biology
Synthetic Biology often lacks the predictive power needed for efficient bioengineering. Here the authors present ART, a machine learning and probabilistic predictive tool to guide synthetic biology design in a systematic fashion.
- Tijana Radivojević
- , Zak Costello
- & Hector Garcia Martin
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Article
| Open AccessThioglycoligase derived from fungal GH3 β-xylosidase is a multi-glycoligase with broad acceptor tolerance
Thioglycoligases have proved useful for bonding carbohydrates to non-sugar acceptors, however, the scope of these biocatalysts is usually limited. Here, the authors engineer a xylosidase into a thioglycoligase with the ability to form O-, N-, S- and Se- glycosides together with sugar esters and phosphoesters.
- Manuel Nieto-Domínguez
- , Beatriz Fernández de Toro
- & María Jesús Martínez
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Article
| Open AccessCombining mechanistic and machine learning models for predictive engineering and optimization of tryptophan metabolism
In metabolic engineering, mechanistic models require prior metabolism knowledge of the chassis strain, whereas machine learning models need ample training data. Here, the authors combine the mechanistic and machine learning models to improve prediction performance of tryptophan metabolism in baker’s yeast.
- Jie Zhang
- , Søren D. Petersen
- & Michael K. Jensen
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