Molecular engineering articles within Nature Communications

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  • Article
    | Open Access

    Major Histocompatibility Complex (MHC) class I molecules present tightly binding peptides on the cell surface for recognition by cytotoxic T cells. Here, the authors present the crystal structures of a disulfide-stabilized human MHC class I molecule in the peptide-free state and bound with dipeptides, and find that peptide binding is accompanied by concerted conformational switches of the amino acid side chains in the binding pockets.

    • Raghavendra Anjanappa
    • , Maria Garcia-Alai
    •  & Rob Meijers

  • Article
    | Open Access

    Cell surface proteins mediate the interactions between cells and their extracellular environment. Here the authors design synthetic biomemetic receptor-like sensors that facilitate programmable interactions between bacteria and their target.

    • Naama Lahav-Mankovski
    • , Pragati Kishore Prasad
    •  & David Margulies

  • Article
    | Open Access

    Bacteria represent an unexploited reservoir of biosensing proteins. Here the authors use genomic screens and functional assays to isolate a progesterone sensing allosteric transcription factor and use a FRET-based method to develop an optical progesterone sensor.

    • Chloé Grazon
    • , R C. Baer
    •  & James E. Galagan

  • Article
    | Open Access

    Directed evolution of the ribosome is challenging because the requirement of cell viability limits the mutations that can be made. Here the authors develop a platform for in vitro ribosome synthesis and evolution (RISE) to overcome these constraints.

    • Michael J. Hammerling
    • , Brian R. Fritz
    •  & Michael C. Jewett

  • Article
    | Open Access

    CRISPR homing gene drives are highly invasive and can fail due to the rapid evolution of resistance. Here the authors present TARE drive, inspired by naturally occurring selfish genetic elements, which is less vulnerable to resistance and can potentially be confined to a target population.

    • Jackson Champer
    • , Esther Lee
    •  & Philipp W. Messer

  • Article
    | Open Access

    Optogenetic tools have been used to control cellular behaviours but their use to probe structure-function relations of signalling proteins are underexplored. Here the authors engineer optogenetic modules into STIM1 to dissect molecular details of STIM1-mediated signalling and control various cellular events.

    • Guolin Ma
    • , Lian He
    •  & Yubin Zhou

  • Perspective
    | Open Access

    Genome-scale engineering requires the integration of a wide range of in silico and in vivo technologies, as well data management procedures and legal infrastructure. Here the authors provide a list of recommendations to address these challenges.

    • Bryan A. Bartley
    • , Jacob Beal
    •  & Elizabeth A. Strychalski

  • Article
    | Open Access

    The physical limits and reliability of PCR-based random access of DNA encoded data is unknown. Here the authors demonstrate reliable file recovery from as few as ten copies per sequence, providing a data density limit of 17 exabytes per gram.

    • Lee Organick
    • , Yuan-Jyue Chen
    •  & Luis Ceze

  • Article
    | Open Access

    Current cellular rewiring designs are typically tailored to detect single inputs. Here the authors present GEARs that function independently of engineered receptor/reporter systems and directly reroute endogenous signaling pathways to alternative genomic loci using dCas9-directed gene expression.

    • Krzysztof Krawczyk
    • , Leo Scheller
    •  & Martin Fussenegger

  • Article
    | Open Access

    Antibodies expressed in the cytosol often form insoluble aggregates, which makes it hard to target intracellular proteins. Here the authors engineer an ultra-stable cytoplasmic antibody (STAND) with a low isoelectric point that can be used in vivo.

    • Hiroyuki Kabayama
    • , Makoto Takeuchi
    •  & Katsuhiko Mikoshiba

  • Article
    | Open Access

    Monomeric near-infrared (NIR) fluorescent proteins (FPs) from bacterial phytochromes bring potential advantages, but their brightness in cells is lower than dimeric NIR FPs. Here the authors develop enhanced monomeric NIR FPs enabling imaging across different scales without the trade-off between brightness and monomeric state.

    • Mikhail E. Matlashov
    • , Daria M. Shcherbakova
    •  & Vladislav V. Verkhusha

  • Article
    | Open Access

    Optogenetic applications in the brain of live animals often require the use of optic fibers due to poor tissue-penetration of blue light. Here the authors present monSTIM1, an improved high sensitivity optogenetic tool able to modulate Ca2+ signaling in the brain of awake mice using non-invasive light stimulation.

    • Sungsoo Kim
    • , Taeyoon Kyung
    •  & Won Do Heo

  • Article
    | Open Access

    DNA strand displacement reactions can be difficult to scale up for computational tasks. Here the authors develop DNA switching circuits that achieve high-speed computing with fewer molecules.

    • Fei Wang
    • , Hui Lv
    •  & Chunhai Fan

  • Article
    | Open Access

    Feedback mechanisms for synthetic gene circuits are necessary to provide robustness to external perturbations. Here the authors validate a biomolecular controller based on a sigma and anti-sigma factor to achieve stable gene expression in the face of external disturbances in an in vitro synthetic gene circuit.

    • Deepak K. Agrawal
    • , Ryan Marshall
    •  & Eduardo D Sontag

  • Article
    | Open Access

    The design of protein assemblies is a major thrust for biomolecular engineering and nanobiotechnology. Here the authors demonstrate a general mechanism for designing allosteric macromolecular assemblies and showcase a proof of concept for engineered allosteric protein assembly.

    • Luis A. Campos
    • , Rajendra Sharma
    •  & Victor Muñoz

  • Article
    | Open Access

    Tightly controlling cell output is challenging, which has limited development and applications of bacterial sensors. Here the authors develop tunable, fast-responding sensors to control production of metabolic pigments and use them to assess zinc deficiency in a low-cost, minimal equipment fashion.

    • Monica P. McNerney
    • , Cirstyn L. Michel
    •  & Mark P. Styczynski

  • Article
    | Open Access

    CRISPR-Cas systems have well characterized, modular structures. Here the authors use that architecture to design a Cas12a library of 560 synthetic chimeras, with altered PAM preferences and specificities.

    • R. M. Liu
    • , L. L. Liang
    •  & R. T. Gill

  • Article
    | Open Access

    Constructing biosynthetic pathways to study and engineer glycoprotein structures is difficult. Here, the authors use GlycoPRIME, a cell-free workflow for mixing-and-matching glycosylation enzymes, to evaluate 37 putative glycosylation pathways and discover routes to 18 new glycoprotein structures

    • Weston Kightlinger
    • , Katherine E. Duncker
    •  & Michael C. Jewett

  • Perspective
    | Open Access

    Synthetic biology uses cells as its computing substrate, often based on the genetic circuit concept. In this Perspective, the authors argue that existing synthetic biology approaches based on classical models of computation limit the potential of biocomputing, and propose that living organisms have under-exploited capabilities.

    • Lewis Grozinger
    • , Martyn Amos
    •  & Angel Goñi-Moreno

  • Article
    | Open Access

    Flexizymes have been used to expand the scope of chemical substrates for ribosome-directed polymerization in vitro. Here the authors deduce design rules of Flexizyme-mediated tRNA acylation that more effectively predict the incorporation of new monomers into peptides.

    • Joongoo Lee
    • , Kenneth E. Schwieter
    •  & Michael C. Jewett

  • Article
    | Open Access

    Lee et al. report an engineered IgG1 Fc domain that behaves like an hFcRn binding pH toggle switch. The authors show that this new half-life extension Fc domain confers improved pharmacokinetics in new humanized knock-in mouse strains that recapitulate the key processes for antibody persistence in circulation.

    • Chang-Han Lee
    • , Tae Hyun Kang
    •  & George Georgiou

  • Article
    | Open Access

    It is difficult to improve the efficacy of oncolytic virotherapy due to immune system responses and limited understanding of population dynamics. Here the authors use synthetic biology gene circuits to control adenoviral replication and release of immunomodulators in hepatocellular carcinoma cells.

    • Huiya Huang
    • , Yiqi Liu
    •  & Zhen Xie

  • Article
    | Open Access

    Antimicrobial peptides (AMPs) are emerging as drug candidates, but the risk of pathogen resistance is not well understood. Here, the authors investigate AMP resistance evolution in E. coli, finding physicochemical features that make AMPs less prone to resistance and no cross- or horizontally-acquired resistance.

    • Réka Spohn
    • , Lejla Daruka
    •  & Csaba Pál

  • Article
    | Open Access

    Cellular systems have numerous mechanisms to control gene expression. Here the authors build a Tet-On system with conditional destablising elements to regulate gene expression and protein stability, allowing fine modulation of mESC signalling pathways.

    • Elisa Pedone
    • , Lorena Postiglione
    •  & Lucia Marucci

  • Article
    | Open Access

    Increasing TCR cell surface expression can potentiate T cell responses to low-concentrations of antigen. Here the authors identify aminoacids in human TCR variable domains that impact its surface expression, and demonstrate how editing these residues can improve T cell activation and effector function without altering antigen specificity.

    • Sharyn Thomas
    • , Fiyaz Mohammed
    •  & Hans J. Stauss

  • Article
    | Open Access

    Conserved regions of the antibody molecule impact its downstream biological effects. Here the authors show that a rigid hinge conformation increases the agonistic activity of CD40 and DR5 antibodies, distinctly from FcγR-binding, suggesting that the hinge and FcR binding regions can be separately modified to optimize therapies.

    • Xiaobo Liu
    • , Yingjie Zhao
    •  & Fubin Li

  • Article
    | Open Access

    Synthetic RNA-based devices can dynamically control a wide range of processes. Here the authors develop a quantitative and high-throughput mammalian cell-based RNA-seq assay to efficiently engineer ribozyme switches.

    • Joy S. Xiang
    • , Matias Kaplan
    •  & Christina D. Smolke

  • Article
    | Open Access

    Ribo-T is a tethered ribosome complex capable of orthogonal ribosome-mRNA functionality, but has low activity. Here the authors evolve new tether designs that support faster growth and increased protein expression.

    • Erik D. Carlson
    • , Anne E. d’Aquino
    •  & Michael C. Jewett

  • Article
    | Open Access

    Titers of monoterpenoids production in yeast are low due to the fact that the geranyl diphosphate (GPP)-based pathway can redirect metabolic fluxes to growth. Here, the authors build an orthogonal pathway by selecting the cis isomer of GPP as an alternative precursor and achieve high titer monoterpene production.

    • Codruta Ignea
    • , Morten H. Raadam
    •  & Sotirios C. Kampranis

  • Article
    | Open Access

    Construction of plasmids from multiple fragments often uses customised parts and leaves scars where fragments are joined. Here the authors develop a method for barcoding fragments and constructing plasmids in a scarless manner from a collection of standard parts.

    • Xiaoqiang Ma
    • , Hong Liang
    •  & Kang Zhou

  • Article
    | Open Access

    Bacillus subtilis has complex spatial and temporal gene expression patterns but currently lacks optogenetic tools to explore these processes. Here the authors import and debug a cyanobacterial green light sensor pathway and show that it enables precise optical control of gene expression.

    • Sebastian M. Castillo-Hair
    • , Elliot A. Baerman
    •  & Jeffrey J. Tabor

  • Article
    | Open Access

    Proteins have been used in the synthesis of magnetic nanoparticles but issues with aggregation limit this application. Here, the authors report on the synthesis of coiled proteins that display the active loop of the natural proteins to avoid aggregation and investigate the application in nanoparticle synthesis.

    • Andrea E. Rawlings
    • , Lori A. Somner
    •  & Sarah S. Staniland

  • Article
    | Open Access

    Metabolic engineering requires the balancing of gene expression to obtain optimal output. Here the authors present COMPASS – COMbinatorial Pathway ASSembly – which uses plant-derived artificial transcription factors and cloning of thousands of DNA constructs in parallel to rapidly optimise pathways.

    • Gita Naseri
    • , Jessica Behrend
    •  & Bernd Mueller-Roeber

  • Article
    | Open Access

    Adoption of DNA as a data storage medium could be accelerated with specialized synthesis processes and codecs. The authors describe TdT-mediated DNA synthesis in which data is stored in transitions between non-identical nucleotides and the use of synchronization markers to provide error tolerance.

    • Henry H. Lee
    • , Reza Kalhor
    •  & George M. Church

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