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  • Journal article
    Sun M, Gao AX, Ye B, Zhao Y, Ledesma-Amaro R, Gao J, Wang Pet al., 2026,

    Advances in engineering and applications of synthetic phase-separated membraneless organelles in biotechnology

    , Synthetic and Systems Biotechnology, Vol: 13, Pages: 37-49, ISSN: 2405-805X

    Membraneless organelles (MLOs) formed through liquid-liquid phase separation (LLPS) constitute crucial dynamic microenvironments within cells, capable of selectively concentrating specific molecules and regulating biochemical reactions. Based on the working mechanisms of natural MLOs, researchers have designed and constructed various synthetic MLOs. These MLOs have been applied in regulating enzyme activity, optimizing metabolic pathways, regulating gene expression, producing recombinant proteins, and developing functional biomaterials. Here, we systematically summarized the design strategies, characterization techniques, and client protein recruitment methods for synthetic MLOs, and categorically reviewed their application progress in the biotechnology field. We also discussed current challenges faced in the practical applications of synthetic MLOs and future research directions. This review aims to provide theoretical guidance and practical reference for the design and application of LLPS-driven synthetic MLOs, thereby promoting their innovative development in synthetic biology and biotechnology.

  • Journal article
    Wang H-Y, Yuen ELH, Chen Y-F, Chiang B-J, Vuolo C, Jenkins SL, King FJ, Lee K-T, Goh F-J, Ibrahim TE, Bozkurt TO, Wu C-Het al., 2026,

    A hydrophobic core in the coiled-coil domain is essential for NRC resistosome function.

    , New Phytol, Vol: 250, Pages: 3247-3263

    The nucleotide-binding leucine-rich repeat protein (NLR) required for cell death (NRC) family represents a group of helper NLRs that are required by sensor NLRs to execute hypersensitive cell death during pathogen infection. NRCs contain an N-terminal coiled-coil (CC) domain essential for their function, yet our knowledge of how this domain contributes to NRC function remains limited. Using site-directed mutagenesis and transient expression in Nicotiana benthamiana, we screened conserved hydrophobic residues among NRCs and identified seven required for NRC4-mediated cell death, revealing a hydrophobic feature within the CC domain that contributes to NRC-mediated immunity. Structural analysis revealed that four of these residues form a hydrophobic core in the CC domain. This hydrophobic core is important for NRC4 subcellular localization, oligomerization, and phospholipid association, but not for NRC4 focal accumulation at the extrahaustorial membrane during Phytophthora infestans infection. Sequence analysis and functional assays revealed that this core is highly conserved in NRCs and some singleton NLRs but has degenerated in NRC-dependent sensor NLRs. Our study identifies a hydrophobic feature in the CC domain of NRCs and reveals its contribution to NLR-mediated immunity.

  • Journal article
    Chen SY, Patranabish S, Weiland K, Jiang Q, Bismarck A, Jourdin L, Masania Ket al., 2026,

    Scalable structural supercapacitors with graphene-modified high-surface-area electrodes

    , Composites Science and Technology, Vol: 279, ISSN: 0266-3538

    Electrification, including emerging technologies such as structural supercapacitors, is critical in realizing carbon-neutral transportation. A fundamental challenge is the trade-off between mechanical properties and energy storage capabilities. We report the fabrication of structural supercapacitors with a novel fibre-fibre interface to improve the interlaminar strength and encapsulation while considering the effect of structural resin on energy storage performance. The synthesized graphene nanoplatelets-modified electrodes attain a high specific surface area of ∼231 m<sup>2</sup> g<sup>−1</sup> - outperforming comparable carbon-based electrodes. We learned that the use of a gel-polymer electrolyte (GPE) separator containing 60 wt% Li-salt eliminates the requirement of electrolyte infusion and showed the highest values for conductivity for the cell produced using GPE. The implementation of glass fabrics (GFs) into the GPE improved the flexural modulus by ∼22%, while retaining the mechanical strength of the cells. The multifunctional performance of the produced SSCs were on par or even outperformed the performances of SSCs reported in literature. A proof-of-concept prototype demonstrates that gel-polymer electrolyte cells can retain charges for longer than those with a glass fibre separator. Cumulatively, these offer the possibility of conventional composite manufacturing techniques to scale-up and eliminate delamination issues arising from different thermal expansion coefficients which also addresses the balance between mechanical stability and electrochemical performance. Our findings support the advancement of durable, lightweight energy storage and delivery systems for sustainable transportation, with potential applications in robotics and wearable technologies.

  • Journal article
    Ledesma Amaro R, 2026,

    PromoterAtlas: decoding regulatory sequences across Gammaproteobacteria using a transformer model

    , Nature Communications, ISSN: 2041-1723

    Recent advances in deep learning, particularly transformer architectures, have improved computational approaches for biological sequence analysis. Despite these advances, computational models for bacterial promoter prediction have remained limited by small datasets, species-specific training, and binary classification approaches rather than comprehensive annotation frameworks. We present PromoterAtlas, a 1.8M parameter transformer model trained on 9M regulatory sequences from 3,371 gammaproteobacterial species. The model demonstrates recognition of various regulatory elements across different species, including ribosomal binding sites, various types of bacterial promoters, transcription factor binding sites, and terminators. Using this model, we developed a whole-genome promoter annotation tool for Gammaproteobacteria, with various levels of validation that support the predictions of promoters associated with different sigma (σ) factors. Furthermore, we show that the model embeddings reflect cross-species evolutionary relationships, clustering promoters by σ factor identity rather than species-specific sequence features. Finally, we show that model embeddings encode regulatory sequence information that enables effective prediction of transcription and translation levels. PromoterAtlas can contribute to our understanding of and ability to engineer bacterial regulatory sequences with potential applications in bacterial biology, synthetic biology, and comparative genomics.

  • Journal article
    Jiang Q, Normand C, Beauchamp F, Beutl A, Hubert O, Bismarck Aet al., 2026,

    Structural composite battery: Reinforced carbon fibre electrodes within a porous polyethersulfone matrix

    , Composites Science and Technology, Vol: 278, ISSN: 0266-3538

    A method to produce multifunctional structural battery composites comprising carbon fibre reinforced anodes and cathodes, and electrolyte filled bicontinuous polymer matrix is disclosed. Lithium iron phosphate (LFP) and lithium titanate (LTO) were deposited onto carbon fibres by electrophoretic deposition (EPD) to produce multifunctional cathodes and anodes, respectively. EPD allowed for an even coating of individual carbon fibres depositing 30 wt% of active materials with respect to carbon fibre current collectors. Carbon fibre reinforced cathode (LFP@CF), separator and anode (LTO@CF) were stacked and impregnated using polyethersulfone (PES) in N-methyl-2-pyrrolidone (NMP) solution; the PES was subsequently precipitated by non-solvent induced phase separation forming a porous high-performance polymer matrix within the stack. The porous matrix binds the carbon fibres and separator while providing sufficient openness for the electrochemical interface. The LFP@CF | separator | LTO@CF/PES assembly had an average Young's modulus of 27 ± 10 GPa and tensile strength of 282 ± 65 MPa. Structural battery composites possessed an energy density of 63 Wh/kg<inf>LFP</inf> or 2 Wh/kg<inf>battery</inf> at charge rate of 0.1C and were able to be cyclically dis/charged for more than 400 h.

  • Journal article
    Zhao Y, Gu H, Ledesma-Amaro R, He L, Liu S, Shi Ket al., 2026,

    Magnetically actuated β-glucosidase immobilized on oak chips for enhanced wine aroma release.

    , Food Res Int, Vol: 231

    β-Glucosidase (BGL) plays a key role in wine aroma enhancement by hydrolyzing glycosidic precursors; however, its application is limited by instability under harsh winemaking conditions. To address this, we developed an integrated biocatalytic system by immobilizing an acid-tolerant BGL onto functionalized magnetic oak chips (NFOak) via oriented Ni2+-histidine coordination. Comprehensive characterization confirmed the fabrication of a porous, magnetic cellulose scaffold. The immobilized BGL exhibited significantly enhanced stability against winemaking stresses (low pH, high ethanol) compared to the free enzyme. Furthermore, magnetic actuation of the biocomposite improved its hydrolytic performance, likely attributed to enhanced mass transfer. When applied to Chardonnay and Marselan wines, the magnetically actuated system effectively hydrolyzed glycosidic precursors, markedly increasing the concentrations of key volatile compounds-such as linalool and ethyl benzoate associated with fruity and floral aroma profiles. The treatment also induced subtle modulations in wine color and phenolic composition. Safety assessments confirmed no nickel leaching and oenologically acceptable iron levels. This work provides a sustainable and efficient strategy for controllable aroma modulation, combining the oenological benefits of a natural oak carrier with the operational controllability of magnetic actuation.

  • Journal article
    Butler L, Awan AR, Ellis T, Akram MSet al., 2026,

    Engineering non-ribosomal peptide synthesis: tuning the antibiotics engine of the microbial world.

    , Crit Rev Biotechnol, Vol: 46, Pages: 501-521

    Non-Ribosomal Peptide Synthetases produce chemically diverse peptides in nature, many of which have antimicrobial properties, providing an opportunity to use synthetic biology to fine tune them for pharmaceutical applications. Major challenges remain with total and semi-synthesis of these complex peptides with specific bioengineering methodologies being developed to increase low yields and enhance bioactivity. Here we review major advances in engineering non-ribosomal peptides with a focus on improvements made to achieve better yield and bioactivity. This can be achieved through: engineering precursor metabolites, altering metabolic flux, introducing strong promoters and regulators, and redirecting metabolism to biosynthetic gene clusters which can then be expressed natively or heterologously. We also review glycopeptide antibiotics as a promising opportunity for engineering through synthetic biology for the biosynthesis of novel non-ribosomal peptides.

  • Journal article
    Williams TJ, Kermani NZ, Gonzales-Huerta LE, Shah A, Adcock IM, Chung KF, Armstrong-James D, UBIORPED Study Groupet al., 2026,

    A Role for Non-Canonical Caspases in Fungal Allergic Airway Disease.

    , Clin Exp Allergy, Vol: 56, Pages: 576-578

    Inhibition of the murine ortholog caspase‐11 reduces neutrophilia and inflammatory cytokine levels. Wedelolactone or its derivatives offer a potential therapeutic approach for mixed or steroid‐resistant inflammation in allergic fungal airway disease.

  • Journal article
    Ibrahim T, King FJ, Toghani A, Wang L, Jenkins S, Yuen ELH, Wang H-Y, Vuolo C, Eilmann N, Adamkova V, Chia K-S, Castel B, Jones JDG, Carella P, Wu C-H, Kourelis J, Kamoun S, Bozkurt TOet al., 2026,

    A helper NLR channels organellar calcium to trigger plant immunity.

    , Science, Vol: 392, Pages: 499-505

    Upon activation, plant nucleotide-binding leucine-rich repeat (NLR) immune receptors are known to assemble into oligomeric resistosomes that insert into the plasma membrane, forming calcium (Ca2+)-permeable channels and triggering immunity. Here, we found that the RPW8-like coiled-coil NLR (CCR-NLR) N requirement gene 1 (NRG1) primarily targets organelles instead of the plasma membrane. Unlike canonical CC-NLRs, activated NRG1 accumulated at the chloroplast envelope and channeled stromal Ca2+ into the cytosol. AlphaFold modeling of the NRG1 resistosome revealed an unusually long amino-terminal membrane-insertion structure that could span the double membrane of the chloroplast. Nanobody-mediated relocalization showed functional membrane specificity: Chloroplast trapping abolished activity of the canonical helper CC-NLR NRC4 but not NRG1. NRG1 orthologs, from nonflowering lineages to angiosperms, targeted chloroplasts, suggesting that organelle-centered defense dates back at least ~360 million years. We propose that CC-NLR diversification has enabled compartment-specific immune signaling to capture diverse Ca2+ stores.

  • Journal article
    Barkoulas M, Grover M, Ippolito D, 2026,

    Worming out defence strategies: mechanisms of immunity through the lens of genetic screens in C. elegans

    , Heredity, ISSN: 0018-067X

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