Article
|
Open Access
Featured
-
-
Article
| Open AccessMulti-condensate state as a functional strategy to optimize the cell signaling output
Biomolecular condensates often appear as a multi-droplet system inside living cells. Here, using multi-scale simulations, the authors show that such configurations are functionally more efficient in catalyzing cell signaling.
- Aniruddha Chattaraj
- & Eugene I. Shakhnovich
-
Article
| Open AccessSpatially and temporally probing distinctive glycerophospholipid alterations in Alzheimer’s disease mouse brain via high-resolution ion mobility-enabled sn-position resolved lipidomics
Dysregulated glycerophospholipid metabolism in the brain is associated with neurodegenerative diseases. Here, the authors present a 4D lipidomics strategy that profiles glycerophospholipids at the sn-position-resolved level, revealing potentially altered remodeling pathways.
- Shuling Xu
- , Zhijun Zhu
- & Lingjun Li
-
Article
| Open AccessHost cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites
Maurizio and Masid et al. identify common host metabolic pathways essential for Plasmodium falciparum and Theileria parasites, revealing potential for developing shared broad-spectrum antiparasitic therapies to more effectively combat these debilitating infections.
- Marina Maurizio
- , Maria Masid
- & Philipp Olias
-
Comment
| Open AccessAutotrophic yeast
Yeast is a widely used cell factory for the conversion of sugar into fuels, chemicals and pharmaceuticals. Establishing yeast as being autotrophic can enable it to grow solely on CO2 and light, and hereby yeast can be used as a wider platform for transition to a sustainable society.
- Jens Nielsen
-
Article
| Open AccessControlled human hookworm infection remodels plasmacytoid dendritic cells and regulatory T cells towards profiles seen in natural infections in endemic areas
Hookworm infection remains a threat to public health where economic factors restrict treatment and lack of effective vaccination have limited successful therapeutic control which results in reinfection in endemic areas. Here the authors use a controlled human hookworm infection model and use high dimensional single cell profiling to show that plasmacytoid dendritic cells and regulatory T cells profiles that resemble those seen during natural infections in endemic areas.
- Mikhael D. Manurung
- , Friederike Sonnet
- & Maria Yazdanbakhsh
-
Article
| Open AccessIntroducing carbon assimilation in yeasts using photosynthetic directed endosymbiosis
Transforming model heterotrophs into autotrophs is usually accomplished by engineering one carbon assimilation pathway and/or employing laboratory evolution. Here, the authors report the engineering of cyanobacterial endosymbionts in yeasts to achieve photosynthetic growth, carbon assimilation and natural products production.
- Yang-le Gao
- , Jason E. Cournoyer
- & Angad P. Mehta
-
Article
| Open AccessEngineered reversible inhibition of SpyCatcher reactivity enables rapid generation of bispecific antibodies
The SpyTag/SpyCatcher protein ligation technology is valuable in many applications, but few methods exist for controlling reactivity. Here the authors report a method for controlling SpyCatcher activity via S-thiolation of engineered cysteines, demonstrating the value of their technology for the rapid generation of bispecific antibodies.
- Christian Hentrich
- , Mateusz Putyrski
- & Francisco Ylera
-
Article
| Open AccessEngineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs
Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Here the authors apply synNotch receptors to spatially control differentiation of endothelial and skeletal muscle cells in a multicellular construct on assorted biomaterials.
- Mher Garibyan
- , Tyler Hoffman
- & Leonardo Morsut
-
Article
| Open AccessGlobal protein turnover quantification in Escherichia coli reveals cytoplasmic recycling under nitrogen limitation
Gupta, Johnson et al. quantify the turnover rates of ~3200 E. coli proteins, demonstrating that cytoplasmic proteins are recycled when nitrogen is limited and that protein degradation rates are generally uncoupled from cell division rates.
- Meera Gupta
- , Alex N. T. Johnson
- & Martin Wühr
-
Article
| Open AccessTerminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors
How lymphoid and myeloid specification occurs in human haematopoietic progenitors is not fully understood. Here the authors perform a proteomic screen on human bone marrow progenitors and suggest TdT+ and CD84- progenitors as lymphoid-primed progenitors with residual myeloid potentials.
- YeEun Kim
- , Ariel A. Calderon
- & Sean C. Bendall
-
Perspective
| Open AccessDeconstructing synthetic biology across scales: a conceptual approach for training synthetic biologists
Developing biotechnologies to address society’s challenges requires integrating concepts across disciplines, posing challenges to educating students with diverse expertise. In this Perspective the authors create a framework for synthetic biology training that deconstructs biotechnologies across spatial scales.
- Ashty S. Karim
- , Dylan M. Brown
- & Julius B. Lucks
-
Article
| Open AccessTunable translation-level CRISPR interference by dCas13 and engineered gRNA in bacteria
It’s difficult to precisely modulate translation-level gene expression using CRISPR-dCas13 due to the lack of detailed characterization of the system. Here, the authors fill the knowledge gap and develop a synthetic tunable Tl-CRISPRi system to enable precise and predictable control of mRNA translation.
- Giho Kim
- , Ho Joon Kim
- & Sang Woo Seo
-
Article
| Open AccessWidespread chromatin context-dependencies of DNA double-strand break repair proteins
DNA double-strand breaks are repaired by multiple pathways. The balance of these pathways depends on the local chromatin context, but the underlying mechanisms are poorly understood. Here the authors uncover a network of proteins that regulate pathway balance in a chromatin context-dependent manner.
- Xabier Vergara
- , Anna G. Manjón
- & Bas van Steensel
-
Article
| Open AccessATP biosensor reveals microbial energetic dynamics and facilitates bioproduction
ATP dynamics influence bioproduction yet are largely unexplored in this context. Here, authors unravel ATP dynamics across various conditions, identify carbon sources which boost ATP levels and bioproduction, and uncover metabolic bottlenecks, shedding light on how ATP dynamics can be used to enhance bioproduction.
- Xinyue Mu
- , Trent D. Evans
- & Fuzhong Zhang
-
Article
| Open AccessA stochastic vs deterministic perspective on the timing of cellular events
Cells exhibit remarkable temporal precision in regulating their internal states. Here, by solving stochastic first passage time problems for key molecular processes Ham, Coomer et al. shed light on how cells achieve this precision.
- Lucy Ham
- , Megan A. Coomer
- & Michael P. H. Stumpf
-
Article
| Open AccessSimultaneous enhancement of multiple functional properties using evolution-informed protein design
A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Here the authors use the evolutionary model EVcouplings to computationally design highly mutated variants of TEM-1 ß-lactamase, and characterise these designs experimentally.
- Benjamin Fram
- , Yang Su
- & Nicholas P. Gauthier
-
Article
| Open AccessProteome allocation is linked to transcriptional regulation through a modularized transcriptome
Here, the authors suggest that bacterial proteomes and transcriptomes can be modularized similarly, revealing previously uncharacterized relationships and opening up the possibility of predicting proteome allocation from transcriptomic data.
- Arjun Patel
- , Dominic McGrosso
- & Bernhard O. Palsson
-
Article
| Open AccessEnhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing
Technologies that generate precise combinatorial genome modifications are well suited to dissect the polygenic basis of complex phenotypes and engineer synthetic genomes. Here the authors systematically optimize eMAGE for enhanced editing efficiency and editing distance and apply these advances to identify genetic factors of nuclear hormone dysfunction.
- Peter N. Ciaccia
- , Zhuobin Liang
- & Farren J. Isaacs
-
Article
| Open AccessDynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling
Studying the impact of SARS-CoV-2 on organelle dynamics may shed more light on the mechanisms of viral replication. Here, the authors combine label-free holotomographic microscopy with AI to study subcellular changes and organelle dynamics upon SARS-CoV-2 infection.
- Nell Saunders
- , Blandine Monel
- & Mathieu Fréchin
-
Article
| Open AccessSpatial multi-omics of human skin reveals KRAS and inflammatory responses to spaceflight
Here the authors profile skin microenvironment changes in response to spaceflight by performing a multi omics analysis using skin punch biopsies from the crew members of SpaceX Inspiration4 mission comparing before, post launch and one day after return 91 of the 3-day mission.
- Jiwoon Park
- , Eliah G. Overbey
- & Christopher E. Mason
-
Article
| Open AccessSpace radiation damage rescued by inhibition of key spaceflight associated miRNAs
In space radiation-exposed cells, targeting specific microRNAs with antagomirs can reduce cardiovascular damage and improve cellular function. Here the authors describe a reduction in inflammation and DNA double-strand break activity within these cells upon antagomir treatment.
- J. Tyson McDonald
- , JangKeun Kim
- & Afshin Beheshti
-
Article
| Open AccessCirculating cell-free RNA in blood as a host response biomarker for detection of tuberculosis
Whole blood signatures have served as the potential biomarkers for TB but failed to meet World Health Organization’s (WHO) optimal target product profiles (TPP). By employing cohorts from multiple countries, the authors identify a diagnostic 6-gene signature from cell free RNA which outperforms TPP requirement in distinguishing TB from non-TB.
- Adrienne Chang
- , Conor J. Loy
- & Iwijn De Vlaminck
-
Article
| Open AccessEmergent digital bio-computation through spatial diffusion and engineered bacteria
Biological computing is a promising field with potential applications in biosafety, environmental monitoring, and personalized medicine. Here the authors create bio-computers using engineered E. coli colonies that respond to chemical gradients, producing different logic functions depending on how they are spatially arranged.
- Alex J. H. Fedorec
- , Neythen J. Treloar
- & Chris P. Barnes
-
Article
| Open AccessAdvanced methods for gene network identification and noise decomposition from single-cell data
To identify intracellular dynamics at the single-cell level, authors develop a scalable method via a divide-and-conquer strategy and apply it to a yeast transcription system. The results underscore the heterogeneity in isogenic cells, which is validated by a noise-decomposition method.
- Zhou Fang
- , Ankit Gupta
- & Mustafa Khammash
-
Article
| Open AccessThe role of promiscuous molecular recognition in the evolution of RNase-based self-incompatibility in plants
Self-incompatibility evolved to avoid self-fertilization among hermaphroditic plants, yet it remains murky how this compatibility recognition evolved. This study constructs a theoretical framework incorporating promiscuous molecular recognition into the evolutionary model of incompatibility.
- Keren Erez
- , Amit Jangid
- & Tamar Friedlander
-
Article
| Open AccessRapid response of fly populations to gene dosage across development and generations
While developmental phenotypes are often multigenic and involve environmental inputs, most research approaches involve perturbation of small numbers of genes. Here they use a synthetic evolution approach in Drosophila to show that adding extra copies of bicoid leads to rapid, system-wide phenotypic responses, potentiated by highly polygenic traits such as embryo size.
- Xueying C. Li
- , Lautaro Gandara
- & Justin Crocker
-
Article
| Open AccessAcute depletion of BRG1 reveals its primary function as an activator of transcription
Here, the authors generate a mouse line by knocking in the auxin-inducible degron tag to the SMARCA4 gene, which encodes BRG1. They suggest that BRG1 primarily contributes positively to chromatin accessibility, RNAP binding, and nascent RNA production.
- Gang Ren
- , Wai Lim Ku
- & Keji Zhao
-
Article
| Open AccessRevealing the mechanism and function underlying pairwise temporal coupling in collective motion
It is known that spatially localized interactions can give rise to self-organized collective motion. Here, by studying pairwise interactions in juvenile zebrafish, authors reveal the role of reciprocal temporal coupling and find that temporal coordination considerably improves spatial responsiveness, such as reacting to changes in the direction of motion of a partner.
- Guy Amichay
- , Liang Li
- & Iain D. Couzin
-
Article
| Open AccessSer/Leu-swapped cell-free translation system constructed with natural/in vitro transcribed-hybrid tRNA set
The use of orthogonal genetic code can help to prevent the escape of hazardous genes through horizontal gene transfer. Here, the authors develop a cell-free translation system with the Ser/Leu-swapped genetic code using a hybrid tRNA set and show its application in enhancing the production of superfolder GFP.
- Tomoshige Fujino
- , Ryogo Sonoda
- & Hiroshi Murakami
-
Article
| Open AccessMAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer
Here the authors apply the Motif Activity on Pre-mRNA Processing (MAPP) tool to standard RNA sequencing data, thereby unravelling the co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer.
- Maciej Bak
- , Erik van Nimwegen
- & Andreas J. Gruber
-
Article
| Open AccessNetwork-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis
Aberrant signalling pathway activity is relevant for tumour growth and resistance to therapy, but remains hard to understand and target. Here, the authors develop VESPA, a phosphoproteomics-based machine learning algorithm that can elucidate response and adaptation to drug perturbations in cancer signalling pathways.
- George Rosenberger
- , Wenxue Li
- & Andrea Califano
-
Article
| Open AccesstauFisher predicts circadian time from a single sample of bulk and single-cell pseudobulk transcriptomic data
There is a need to determine circadian time in gene expression datasets. Here, authors built tauFisher, a pipeline that predicts circadian time labels from single transcriptomic samples. tauFisher will be useful for determining body clock time in circadian medicine and for research.
- Junyan Duan
- , Michelle N. Ngo
- & Bogi Andersen
-
Perspective
| Open AccessEngineering is evolution: a perspective on design processes to engineer biology
Evolutionary and rational design approaches are commonly used to engineer biological systems but are typically seen at odds with each other. In this perspective the authors argue for the concept of an evolutionary design spectrum to help unify and compare these design methodologies to support more effective biological engineering.
- Simeon D. Castle
- , Michiel Stock
- & Thomas E. Gorochowski
-
Article
| Open AccessEfficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform
Paralog synthetic lethals have been assessed with multiple CRISPR-based methods, but systematic comparison among these platforms is unavailable. Here, the authors systematically compare combinatorial perturbation platforms and establish the in4mer CRISPR/Cas12a multiplex knockout platform.
- Nazanin Esmaeili Anvar
- , Chenchu Lin
- & Traver Hart
-
Article
| Open AccessHuman connectome topology directs cortical traveling waves and shapes frequency gradients
The factors that determine the direction of traveling waves in the brain are not well understood. Here, the authors show that the sum of incoming structural connection strengths shape both traveling wave direction and frequency gradients.
- Dominik P. Koller
- , Michael Schirner
- & Petra Ritter
-
Article
| Open AccessDisordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator
Many clock proteins contain intrinsically disordered regions, but how these regions mediate protein interactions is poorly understood. Here, the authors identify charge blocks within a disordered clock protein that regulate circadian timing.
- Meaghan S. Jankowski
- , Daniel Griffith
- & Jennifer M. Hurley
-
Article
| Open AccessTemporal coordination of the transcription factor response to H2O2 stress
H2O2 stress is known to activate a slew of transcription factors that restore redox balance. Here, the authors use live-cell imaging and single-cell analysis to reveal that the transcription factors that are activated and their timing of activation is dose dependent.
- Elizabeth Jose
- , Woody March-Steinman
- & Andrew L. Paek
-
Article
| Open AccessCell-type-specific mRNA transcription and degradation kinetics in zebrafish embryogenesis from metabolically labeled single-cell RNA-seq
This study analyzes the embryonic replacement of maternally contributed mRNA with new mRNA in single cells and shows dynamic spatio-temporal regulation of maternal mRNA decay and cell-type specific retention within the earliest specified cell types in zebrafish embryos.
- Lior Fishman
- , Avani Modak
- & Michal Rabani
-
Article
| Open AccessDecoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis
Elucidating the gastroesophageal junction’s development is key to comprehending its disease susceptibility. Here, the authors mapped its development, uncovering cellular diversity and interaction dynamics using advanced spatiotemporal single-cell analysis.
- Naveen Kumar
- , Pon Ganish Prakash
- & Cindrilla Chumduri
-
Article
| Open AccessSpatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones
Intratumoural heterogeneity in high-grade serous ovarian carcinoma (HGSOC) remains to be explored. Here, the authors perform spatial transcriptomics and reveal a high degree of subclonal heterogeneity in HGSOC.
- Elena Denisenko
- , Leanne de Kock
- & Alistair R. R. Forrest
-
Article
| Open AccessA lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis
By tracing promoter expression in lineage-mapped single cells, Xu et al. present a whole-body cartography of microRNA transcriptional activities during C. elegans embryogenesis and demonstrate its broad utility in multifaceted functional analyses.
- Weina Xu
- , Jinyi Liu
- & Zhuo Du
-
Perspective
| Open AccessEngineering biology and climate change mitigation: Policy considerations
Engineering biology is a dynamic field that uses gene editing, synthesis, assembly, and engineering to design new or modified biological systems. Here the authors discuss the policy considerations and interventions needed to support a role for engineering biology in climate change mitigation.
- Jonathan Symons
- , Thomas A. Dixon
- & Isak S. Pretorius
-
Article
| Open AccessMutational scanning pinpoints distinct binding sites of key ATGL regulators in lipolysis
ATGL is a key enzyme in intracellular lipolysis. Here, the authors use deep mutational scanning to define the determinants of protein interaction between ATGL and its regulatory partners, gaining insights into lipolysis mechanisms in cells.
- Johanna M. Kohlmayr
- , Gernot F. Grabner
- & Ulrich Stelzl
-
Article
| Open AccessEngineering intelligent chassis cells via recombinase-based MEMORY circuits
The unification of decision-making, communication, and memory would enable the programming of intelligent biotic systems. Here, the authors achieve this goal by engineering E. coli chassis cells with an array of inducible recombinases that mediate diverse genetic programs.
- Brian D. Huang
- , Dowan Kim
- & Corey J. Wilson
-
Article
| Open AccessPopulation-wide cerebellar growth models of children and adolescents
The development of the human cerebellum is not well understood. Here, the authors analyse a large sample of neuroimaging scans from children and adolescents to develop growth models of the cerebellum which mirror age-related developmental trajectories of behaviour and function.
- Carolin Gaiser
- , Rick van der Vliet
- & Ryan L. Muetzel
-
Article
| Open AccessA universal system for boosting gene expression in eukaryotic cell-lines
Production of proteins at scale and affordable cost has been a major need of the biotech sector for the last several decades. Here the authors present a design algorithm called UNILIB for boosting gene expression in eukaryotic cells developed using an oligo-library and machine learning approach, validated in both yeast and mammalian cells using unseen sequences.
- Inbal Vaknin
- , Or Willinger
- & Roee Amit
-
Article
| Open AccessSpyMask enables combinatorial assembly of bispecific binders
Bispecific antibody architecture is often important for function but rarely optimized. Here, authors present a modular approach to assemble bispecifics in varied formats using a SpyTag/SpyCatcher approach called SpyMask, and build anti-HER2 bispecifics whose activities depend on binder orientation and bispecific geometry.
- Claudia L. Driscoll
- , Anthony H. Keeble
- & Mark R. Howarth
-
Article
| Open AccessCRISPR-powered quantitative keyword search engine in DNA data storage
Targeting the files containing content-of-interest is a challenge in DNA data storage. Here, the authors develop a CRISPR-powered search engine to quantitatively identify the keyword in files stored in DNA.
- Jiongyu Zhang
- , Chengyu Hou
- & Changchun Liu
-
Article
| Open AccessA citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations
While tricarboxylic acid cycle (TCA cycle) is required for heterotrophic microbes, it reduces carbon yield of industrial products due to the release of excess CO2. Here, the authors construct an E. coli strain without a functional TCA cycle and demonstrate its feasibility as a chassis strain for production of four separate compounds.
- Hang Zhou
- , Yiwen Zhang
- & Baixue Lin
Browse broader subjects
Browse narrower subjects
- Bayesian inference
- Biobricks
- Biochemical networks
- Bioenergetics
- Cellular noise
- Complexity
- Computer modelling
- Computer science
- Control theory
- Criticality
- Differential equations
- DNA computing and cryptography
- Dynamic networks
- Dynamical systems
- Emergence
- Evolvability
- Genetic circuit engineering
- Genetic interaction
- Genomic engineering
- Information theory
- Logic gates
- Metabolic engineering
- Modularity
- Molecular engineering
- Molecular fluctuations
- Multicellular systems
- Multistability
- Nonlinear dynamics
- Numerical simulations
- Oscillators
- Population dynamics
- Programming language
- Protein engineering
- Regulatory networks
- Reverse engineering
- Robustness
- Signal processing
- Single-cell imaging
- Software
- Standardization
- Stochastic modelling
- Stochastic networks
- Synthetic biology
- Systems analysis
- Time series