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  • Journal article
    Hui T-Y, Epopa PS, Millogo AA, Yao FA, Koulmaga D, Noulin F, Diabate A, Burt Aet al., 2026,

    Variance partitioning reveals contrasting random effect contributions to the density and species composition of malaria-transmitting mosquitoes in Western Burkina Faso

    , Parasites and Vectors, Vol: 19, ISSN: 1756-3305

    Background Spatial-temporal variation exists in the density and species composition of malaria-carrying mosquitoes, which will in turn influence the transmission of the disease. While there has been extensive research on seasonality and other main drivers of the vector populations, the heterogeneity partitioned as random effects at various spatial-temporal scales is just as important but has not attracted the same attention. Methods To investigate the relative contributions of the between-house, between-village, and between year variations, as well as other house-level covariates such as inhabitant number and bed net usage on vector density and species composition, intensive Pyrethroid Spray Catches (PSC) sampling was conducted across a 60-month period between 2012-2019 from four villages in the Sudano-Sahelian region of Burkina Faso. Results For density, measured by female Anopheles gambiae s.l. counts, our modelling showed that the between-house variation was the largest variance component, followed by the between year then between-village variation, after accounting for seasonality and other covariates. Density increased with the number of inhabitants within a household but was uncorrelated with bed net presence. A subset of female mosquitoes was genotyped for species identification, and the composition of An. coluzzii and An. gambiae, the two dominant vectors in the region, varied markedly across villages without an overall trend. The between-village variance contributed up to 76% of the total random variation in species composition, followed by the between-year variance. The between-house variation was statistically insignificant. Neither household size nor bed net usage had any impact on species composition. Conclusions Interestingly, the between-house component of variation was the largest contributor when measuring mosquito density, but it was the least important for species composition. For between-village variation the converse was found. Together with
  • Journal article
    Maia RA, Oki Y, Medina I, Figueiredo JCG, Barbosa M, Pereira EG, Aguirre-Gutiérrez J, Fernandes GWet al., 2026,

    Atlantic forest tree enhances photoprotective and thermotolerance in soils contaminated by mining tailings

    , Theoretical and Experimental Plant Physiology, Vol: 38

    Large-scale mining disasters in tropical regions impose long-term pressures on ecosystems by degrading soil fertility and exposing native vegetation to chemical and physical disturbances. This study investigates whether Eugenia florida, a native tree species found in both tailings-impacted and reference areas of the Rio Doce Basin in Brazil, exhibits physiological adjustments that confer resilience to combined edaphic and thermal constraints. We assessed soil properties and 16 physiological traits related to nutrient status, photosynthetic efficiency, photoprotection, and thermal tolerance. Soils in the impacted area exhibited markedly lower organic matter, cation exchange capacity, and nutrient concentrations, along with increased iron concentration. Despite a 10% reduction in nitrogen balance index, plants in the impacted area exhibited 10% more chlorophyll and 19% more flavonoids, indicating compensatory pigment production and enhanced antioxidant capacity. Photosynthetic performance remained stable across environments, but individuals in the impacted area displayed elevated regulated energy dissipation and reduced unregulated energy loss, suggesting efficient photoprotective adjustments. Transient fluorescence analyses revealed intensified excitation fluxes and greater heat dissipation per reaction centre. Thermal thresholds, defined as temperatures causing 15% and 50% reductions in photosynthetic efficiency, were significantly higher in impacted individuals. Multivariate analyses identified excitation flux traits as key predictors of thermal resilience. Physiological function in E. florida is sustained through integrated plastic responses under long-term soil degradation and thermal constraints. Its ability to modulate energy fluxes and antioxidant defences highlights its potential as a candidate species for ecological restoration in tropical regions increasingly affected by human disturbance and climate extremes.
  • Journal article
    Wan Y, Wong JLC, Sanchez-Garrido J, Low WW, Turton JF, Morecchiato F, Baccani I, Dodgson K, Rossolini GM, Woodford N, Frankel G, Jauneikaite E, Meunier D, Hopkins KLet al., 2026,

    Genomic and molecular characterisation of a KPC-producing Klebsiella pneumoniae clinical isolate resistant to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam

    , BMC Genomic Data, Vol: 27, ISSN: 2730-6844

    Background Resistance to carbapenems and third-generation cephalosporins is increasing in Klebsiella pneumoniae globally, restricting therapeutic options. The β-lactam/β-lactamase inhibitor combinations are widely used to circumvent β-lactamase-mediated resistance. In 2021, an unusual K. pneumoniae clinical isolate, KpMVR1, was recovered from a hospitalised patient in England, exhibiting resistance to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam. To investigate this phenomenon, we characterised the genome and antimicrobial susceptibility of KpMVR1 alongside two clonally related isolates susceptible to all three β-lactam/β-lactamase inhibitor combinations: KpMVS1, collected from the same patient 42 days earlier, and KpMVS2, from another patient in the same hospital. Methods Illumina and MinION whole-genome sequencing were conducted for these three isolates, followed by hybrid genome assembly. Annotated genome assemblies were compared to identify genetic variation. Mutagenesis experiments were performed to verify predicted functional alterations. Results All isolates belonged to clone ST8134 and carried blaKPC-2 alleles (KpMVR1: blaKPC-157; KpMVS1 and KpMVS2: blaKPC-2) in plasmids predicted to be conjugative. Insertion sequence ISEc68 caused a frameshift mutation in KpMVR1’s ompK36 gene, reducing susceptibility to meropenem-vaborbactam and imipenem-relebactam. KPC-157 demonstrated decreased hydrolysis of imipenem and ceftazidime when compared with KPC-2. KpMVR1 also encoded a disrupted transcriptional repressor MarR and a destabilising mutation in AcrB, a component of the AcrAB-TolC multidrug efflux pump. An intact, iron-transporting fec operon was identified on a novel IncFII(pKP91)/IncFIB(K) plasmid unique to KpMVS2, possibly accounting for the cefiderocol resistance observed in this isolate. ConclusionsKpMVR1 carried multiple resistance-associated genetic alterations and likely developed its resistance profile
  • Journal article
    De Lorm TA, Heon SP, Bernard H, Ewers RMet al., 2026,

    Bird and mammal communities transform without collapsing in response to oil palm replanting

    , Forest Ecology and Management, Vol: 619, ISSN: 0378-1127

    Replanting a tree plantation - that is, clearing old trees and replacing these with young plants - drastically alters its habitat structure and microclimate, leading to changes in its biodiversity. Nevertheless, we lack an understanding of how the replanting of oil palm plantations - the most prominent oil crop globally - affects mammals and birds, while the amount of area replanted will increase exponentially over the next decades. We therefore studied how the bird and mammal community of an oil palm plantation in Malaysian Borneo changed in response to replanting. Using camera traps for mammals, and acoustic recordings and BirdNET for birds, we show that both communities are transformed. Mammal species richness slightly dropped, because of the absence from replanted plantations of long- and pig-tailed macaques (Macaca fascicularis and M. nemestrina), both endangered primate species. Bird species richness did not significantly differ between replanted and mature plantations. However, the detection frequency of most species changed, as the bird community shifted from forest and woodland species towards open-habitat species. The detection frequency and species richness of different trophic niches stayed largely constant, indicating that birds will still be able to perform similar high-level ecological functions in replanted plantations. Overall, our results show that replanting reshaped mammal and bird communities, but that their diversity and abundance does not collapse. These findings stress the importance of staggered replanting, as opposed to replanting large stretches of plantation in one go, to bolster landscape level biodiversity, and underscore that tree plantations are temporally dynamic habitats.
  • Journal article
    Zhao H, Pye R, Walker G, Tran W, Simmonds O, Tsitsa I, Islam S, Hanna G, David Aet al., 2026,

    Missense3D-PTMdb: a web tool for visualising and exploring human genetic variants and post-translational modification sites using alphafold models

    , Journal of Molecular Biology, Vol: 438, ISSN: 0022-2836

    Only a fraction of the >11 million missense variants identified in humans has a known clinical significance. Post-translational modifications (PTMs), such as phosphorylation, glycosylation and ubiquitination, are key regulators of protein function and structure. PTMs depend on correct protein folding and the recognition and binding of enzymes to specific amino acid motifs near modification sites. AlphaFold models provide an unprecedented opportunity to explore variants on 3D structures, enabling systematic identification of amino acid substitutions that could affect PTMs and should be further investigated experimentally.We present Missense3D-PTMdb, a “one-stop-shop” interactive web tool that provides a user-friendly sequence-structure mapping of 20,235 human proteins, 11,5 million naturally occurring human missense variants, >60 PTM types and 203,775 PTM residues and their neighbours in sequence and 3D structure space using AlphaFold models of the human proteome. The resource also supports visualisation of novel variants not in the database. Missense3D-PTMdb is freely available at https://missense3d.bc.ic.ac.uk/ptmdb.
  • Journal article
    Casadio R, Lu ZJ, Mathews DH, Sternberg MJEet al., 2026,

    Computational Resources for Molecular Biology 2026.

    , J Mol Biol, Vol: 438
  • Journal article
    Conev A, Islam SA, Tsitsa I, David A, Sternberg MJEet al., 2026,

    3DSeqCheck: a web-based tool for verifying sequence consistency between a 3D structure file and the corresponding UniProt entry

    , Journal of Molecular Biology, Vol: 438, ISSN: 0022-2836

    UniProt is a central repository of protein sequences and annotations, with entries being updated several times a year as new sequencing evidence is collected. By contrast, protein structure resources often evolve at a different pace. The AlphaFold database remained unchanged for four years, until September 2025, during which time nearly 3% of the associated sequences underwent revisions in UniProt. In a range of bioinformatics tasks, protein structure data is paired with sequence annotations from UniProt. Mapping annotations to outdated structure files can lead to errors in downstream analysis. While this concern has been addressed for experimental structures, efforts for the modeled structures are lacking. 3DSeqCheck is a lightweight web tool that enables quick comparison of the sequence of modeled and experimental structures to the latest UniProt entries. 3DSeqCheck provides an interactive visual panel of the alignment and the comparison of the residue numbering and can be accessed freely at: https://missense3d.bc.ic.ac.uk/3dseqcheck and https://github.ic.ac.uk/ImperialCollegeLondon/check3Dseq.
  • Journal article
    Yi L, Kulik N, Shao S, Nixon PJ, Komenda J, Krynická V, Yu J, Liu Bet al., 2026,

    The transmembrane domain is a primary determinant of the location and substrate specificity in cyanobacterial FtsH heterocomplexes

    , Algal Research, Vol: 98, ISSN: 2211-9264

    Membrane-embedded FtsH proteases play important and diverse physiological roles in prokaryotes, chloroplasts and mitochondria, but how substrates are distinguished remains unclear. The cyanobacterium Synechocystis sp. PCC 6803 contains four FtsH homologs organized into two distinct heterocomplexes and one homocomplex. The two heterocomplexes, derived from a recent gene duplication event, are the essential FtsH1/3 complex found in the cytoplasmic membrane, and the thylakoid-embedded FtsH2/3 complex, with a role in the repair of photodamaged photosystem II. Using a domain swapping approach, we demonstrate here that the transmembrane domains of FtsH1 and FtsH2 are primary determinants of the cellular location and functional differences between the FtsH1/3 and FtsH2/3 complexes, whereas the soluble AAA+ (ATPases associated with diverse cellular activities) and protease domains and the soluble linker were largely interchangeable under the conditions tested. Overall, our findings identify the transmembrane domain as an important determinant of both the location and substrate specificity of FtsH heterocomplexes and support a role for this domain in their functional evolution.
  • Journal article
    Rowell J, Yanez DC, Ross S, Lau C-I, Zhang E, Monfared A, Peña OA, Chain B, Crompton Tet al., 2026,

    The Thymic Microenvironment Shapes Age-Related Qualitative Changes in the TCR Repertoire.

    , Aging Cell, Vol: 25

    Ageing impairs immune function, increasing susceptibility to infection, autoimmunity and inflammation. The thymus undergoes involution during childhood, and thymocyte and thymic epithelial cell (TEC) numbers decline. Given that adaptive immunity depends on T-cells recognising diverse antigens via their unique T-cell receptor (TCR), the precise age-related changes in TCR repertoire composition are key to understand immunity. To investigate the influence of age on the thymic TCR repertoire we sequenced TCRα and TCRβ transcripts from developmentally defined thymocyte populations from 4-week, 12-month and 18-month-old mice, and from thymocytes recovering from hydrocortisone-treatment, and athymic recipients of RAG1-deficient thymus transplants. The 18-month thymus selected TCR repertoires with distinctive patterns of VxJ and CDR3 k-mer usage compared to young thymus, indicating it had a qualitatively different repertoire with different specificity. It also selected a less diverse TCRβ repertoire with more expanded clones than young thymus. On recovery from hydrocortisone-treatment, both 4-week and 12-month thymus showed bias towards foetal-like 3'TRAVx5'TRAJ rearrangements, but 12-month thymus also produced less diverse and evenly distributed TCRβ repertoires, with increased expansion of TCRβ clones at the CD4-CD8-CD25+CD44-intracellularTCRβ+ stage, increased TRBJ-1-cluster usage and distinctive patterns of combinatorial VxJ usage. Transplantation of athymic nude recipients with old RAG1-deficient thymus generated less diverse, less evenly distributed TCR repertoires with different combinatorial VxJ usage than those generated by young transplants. Taken together our experiments show that the old thymus generates qualitatively different TCR repertoires than young thymus and the non-lymphoid compartment of the thymus contributes strongly to these changes and to age-associated decline in TCR repertoire diversity.
  • Journal article
    Godson A, Eddie L, Schuster M, Zheng K, Toth R, Li Y, Li T, Huang J, Kaschani F, Jutras PV, Kourelis J, Kaiser M, Bozkurt T, Van der Hoorn RALet al., 2026,

    NbRD21 protease controls receptor kinase homeostasis in Nicotiana benthamiana.

    , New Phytol, Vol: 251, Pages: 2741-2752

    RD21-like proteases are papain-like cysteine proteases with a C-terminal granulin domain that are abundant and ubiquitous in angiosperms and have often been implicated in immunity. We previously found that the activity of RD21 in Nicotiana benthamiana (NbRD21) is suppressed during infection with Pseudomonas syringae. Here, we studied the role of NbRD21 in immunity and proteome processing. NbRD21 was disrupted by genome editing and rd21 mutants were subjected to disease assays and shotgun proteomics. Dipeptide substrate zLR-AMC was used in protease assays and agroinfiltration was used to transiently express NbRD21 and candidate substrates. Genome-edited lines lacking NbRD21 develop normally but have drastically reduced zLRase activity and are significantly more susceptible to P. syringae. Shotgun proteomics revealed an increased accumulation of c. 20 diverse receptor-like kinases (RLKs) in untreated rd21 knockout lines, but their transcript levels are unaltered when compared to wild-type plants. 35S-driven GFP-tagged RLKs accumulate more upon transient expression in rd21 plants than in wild-type plants. These data indicate that NbRD21 post-translationally controls RLK homeostasis, either by directly degrading RLKs or indirectly by regulating endocytic RLK recycling.
  • Journal article
    Granville NR, Williams JJ, Groner VP, Barlow J, Betts MG, Daskalova GN, Ewers RM, Dos Anjos L, Arroyo-Rodriguez V, Barbaro L, Cerezo A, Develey PF, Hatfield JH, Jactel H, Karubian J, Kormann UG, Lasky JR, Marsh CJ, Mestre LAM, Morante-Filho JC, Olivier P, Phalan BT, Pidgeon AM, Proença V, Terraube J, Uezu A, Wood EM, Pigot AL, Banks-Leite Cet al., 2026,

    Temperature mediates variation in avian sensitivity to forest cover.

    , Nat Ecol Evol

    Emerging evidence shows that responses to deforestation can differ both across species and among populations of the same species. The reasons underlying these complex patterns are unclear, and this lack of clarity is a barrier to accurate monitoring and prediction of biodiversity change. Using data from 2,262 bird species across 7,326 sites from all forested continents, we show that between-species and within-species variations in responses to forest cover are mediated by temperature. Populations in warmer macroclimates tend to decline in incidence in deforested landscapes because hotter microclimates push them closer to their species' realized upper thermal tolerance limits. By contrast, populations in cooler macroclimates tend to be less affected by or even benefit from deforestation, as microclimatic temperatures are pushed closer to more optimal temperatures. Our findings offer an empirically grounded framework for biodiversity models that move beyond fixed species responses and incorporate interactions between temperature and land-use change.
  • Journal article
    Murray JW, 2026,

    Random repeats open a route into folded protein space

    , Proceedings of the National Academy of Sciences, Vol: 123, ISSN: 0027-8424
  • Journal article
    Ellis HR, Behrends V, Larrouy-Maumus G, McQuail J, Wigneshweraraj Set al., 2026,

    Correction for Ellis et al., “Glutathione impacts Hfq condensation in nitrogen-starved <i>Escherichia coli</i> ”

    , Journal of Bacteriology, ISSN: 0021-9193
  • Journal article
    Liu H, Prentice IC, Morfopoulos C, 2026,

    Tracing Vegetation Stress from Space: Isoprene Emissions Capture the Spatiotemporal Footprint of El Niño

    , npj Climate and Atmospheric Science, ISSN: 2397-3722

    El Niño events exert a profound influence on the global carbon cycle by imposing widespread heat and water stress on terrestrial ecosystems. Plant isoprene emissions respond rapidly to such stress, yet it remains unclear whether this response can track the spatiotemporal evolution of El Niño’s impacts over land. Here, we used satellite-derived global isoprene emissions for the first time to assess the west-east progression of the 2015–2016 El Niño. We observed that isoprene emissions increased by up to approximately 30% across tropical ecosystems relative to the climatological mean, with pronounced anomalies emerging during the event. The spatiotemporal evolution of these anomalies closely aligns with the El Niño progression inferred from sea surface temperature (SST) anomalies in the equatorial Pacific. In contrast, commonly used satellite vegetation products, including leaf area index (LAI) and solar-induced chlorophyll fluorescence (SIF), show weaker and spatially incoherent responses. These results demonstrate that satellite-derived isoprene provides a sensitive and mechanistically grounded tracer of ecosystem stress, offering a complementary perspective for monitoring the intensity and propagation of extreme climate events across terrestrial ecosystems.
  • Journal article
    Bergum M, Martin B, Sutton M, Moore Set al., 2026,

    A liquid handling platform for standardised quantification of cell-free enzymatic activity encoded by antimicrobial resistance genes

    , Synthetic Biology, ISSN: 1939-7267

    Antimicrobial resistance (AMR) is a growing global threat to human health, and rapid methods for characterising emerging antimicrobial resistance genes (ARGs) are needed. Here, we develop a semi-automated workflow using cell-free gene expression (CFE) systems to measure the activity of two ARGs encoded on plasmid DNA that produce rifampicin-inactivating and gentamicin-inactivating enzymes. We validated the use of a small benchtop Myra liquid handling system compared to manual pipetting, with no statistical differences observed. After optimising the pre-incubation time of ARGs and dispensing protocol, expression of aac(3)-IIa increased the half-maximal inhibition concentration (IC50) of gentamicin by over 150-fold, while arr-3 increased the IC50 of rifampicin by approximately 20-fold compared to controls. This methodology for rapid, semi-automated ARG characterisation offers a strategy to combat AMR by assessing novel ARGs identified through genomic surveillance or profiling activity of new or derivative antibiotics.
  • Journal article
    Baizurah SN, Groner VP, 2026,

    Conservation: When extremes meet rarity.

    , Curr Biol, Vol: 36, Pages: R919-R921

    A catastrophic five-day rain triggered over 50,000 landslides across the core habitat of the critically endangered Tapanuli orangutan in Sumatra, potentially killing a significant proportion of the population and raising urgent questions about rare species' viability in a changing climate.
  • Journal article
    Ovwemuvwose J, Prentice IC, Graven HD, 2026,

    Uncertainty in land carbon fluxes simulated by CMIP6 models from treatments of crop distributions and photosynthetic pathways

    , Biogeosciences, Vol: 23, Pages: 5593-5605, ISSN: 1726-4170

    A reliable representation of the diversity of vegetation in terrestrial ecosystems is needed for the accurate simulation of present and future biogeochemical cycling and global climate, particularly as climate change affects different vegetation types differently. We compare the distributions of crops and of C3 versus C4 photosynthetic pathways in both natural vegetation and crops across Earth System Models in the 6th Coupled Model Intercomparison Project (CMIP6). We find a large range in C3 and C4 crops, natural and total vegetation for area and gross primary production (GPP) across the models. Even though 10 of the11 models used Land Use Harmonisation (LUH2) crop areas as input data, modelled total crop area ranges from -28 to +10 % of a satellite-based estimate. The C3 and C4 crop areas were -56 to +15 % and -100 to +38 % of LUH2 for 2014, respectively. The C4 fraction of total vegetation area in the models is 9-25 %, compared to 20 ± 3 % in observation-based estimates for the year 2014. Total global GPP varies by a factor of two across the models, and the C4 fraction of GPP ranges from 12 to 27 %. Simulated trends in the fraction of GPP by C3 versus C4 vegetation type (-20 to +29 %) would have changed global stable carbon isotopic discrimination by -0.35 to +0.11 ‰ over 1975-2005, not including changes in discrimination over time within C3 and C4 vegetation, indicating that modeled changes in the fraction of GPP by C3 and C4 vegetation do not account for the +0.7 ‰ increase indicated by atmospheric data. Disparity in vegetation with these photosynthetic pathways in models contributes to uncertainty in land carbon flux simulations, and further constraints and improvements in models are needed.
  • Journal article
    Di Domenico F, Kucharczyk MW, Patel R, Bannister Ket al., 2026,

    Perioperative pregabalin does not alter behavioural or diffuse noxious inhibitory control responses in 2 rat models of chronic pain

    , PAIN Reports, Vol: 11

    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Introduction:</jats:title> <jats:p>Multiple mechanisms contribute to the experience of pain where the use of model organisms to dissect mechanistically sensory regulatory circuitry is a vital component of discovering underlying causes of persistent pain in disease states. Such disease states can be modelled in animals using surgical procedures that, ethically, should involve administration of analgesia. However, since basic pain researchers often wish to measure pain-related events, animals may be denied perioperative analgesia to avoid adversely influencing experimental outcomes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>We conducted a structured review of perioperative analgesia usage in rat spinal nerve ligation (SNL) and cancer-induced bone pain (CIBP) models. Using a combination of behavioural testing and in vivo electrophysiology in the dorsal horn of the spinal cord, we assessed the impact of perioperative pregabalin on nociceptive behaviours in the acute recovery phase, and behavioural and electrophysiological experimental outcomes in the established phase, of rat SNL and CIBP models.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>A literature search revealed that, for studies using rat models of SNL or CIBP, only 5.37% and 12.69%, respectively, reported the use of perioperative analgesia. We then demonstrated that the use of pregabalin as a perioperative analgesic reduced mechanical hypersensitivity in the acute period after SNL surgery, with no impact on behavioural, electrophysiological, or neuropharmacological outcomes in the established p
  • Journal article
    Mullin V, Hana M, Gill R, Ian Bet al., 2026,

    Museum specimens reveal the genomic consequences of long-term population decline in an insect pollinator

    , Molecular Biology and Evolution (MBE), ISSN: 0737-4038
  • Journal article
    Kütahya C, Pániker CC, Ly F, Jerath A, Little E, Gali R, Haimi MZBD, Malek AHBA, Muhamad KB, Supian SB, Young TB, Lawrence S, Bell T, Nee TY, Jiménez JI, Huynh Fet al., 2026,

    Masterbatch-enabled acceleration of polyolefin biodegradation under open air terrestrial environmental conditions

    , npj Materials Degradation, Vol: 10, ISSN: 2397-2106

    Polyolefins, commonly used in packaging and single-use products, are notoriously persistent in the environment, contributing significantly to environmental pollution. In scientific literature to date, polyolefins have not been reported to fully biodegrade. This study examines the biodegradation potential of polyolefin materials, specifically polyethylene (PE) and polypropylene (PP), enhanced through the incorporation of Biotransformation Masterbatch technology. The inclusion of the Biotransformation Masterbatch accelerated and enabled the full biodegradation of PE and PP, as demonstrated by laboratory weathering, and biodegradation studies in soil at mesophilic temperatures. Ecotoxicity tests revealed no adverse effects on test organisms in both soil and water environments, while metagenomics analysis demonstrated that biodegradation of these polyolefins did not significantly change the soil microbiota composition, which showed higher metabolic activity compared to virgin plastic controls. These findings demonstrate that Biotransformation technology provides an effective solution for delivering polyolefin-based materials with reduced environmental impact. It offers a sustainable alternative to conventional plastics, preserving the performance characteristics of traditional polyolefins while addressing the problem with fugitive plastic waste in the environment.
  • Journal article
    Zhu Z, Wang H, Zhou B, Cai W, Harrison SP, De Kauwe MG, Prentice ICet al., 2026,

    Optimal canopy light-use strategy shapes global greenness dynamics

    , Nature Communications, ISSN: 2041-1723

    “Greenness” is a key indicator of the functional state of vegetation. However, the physiological processes behind seasonal patterns in greenness are diverse and incompletely understood, hindering the predictability of climate-driven shifts in global foliage phenology. Optimality principles suggest that plants invest in canopy architecture to maximize light capture. Therefore, we hypothesize that, irrespective of specific physiological mechanisms, greenness (fAPAR: fractional canopy light absorption) commonly tracks the seasonal dynamics of potential production (A0: theoretical canopy carbon uptake with all light absorbed). In other words, plants tend to display foliage when it is most productive. We show that observations confirm this hypothesis and develop a model predicting fAPAR from the seasonal cycle of A0, with a phenological lag that increases (from 2 weeks to 3 months) with increasing moisture. This model captures 81% of observed variations in fAPAR and shows that light and environmentally regulated biophysical constraints shape global patterns of vegetation greenness, its seasonal cycle, and its recent increase.
  • Journal article
    Ghosh M, Goodman D, 2026,

    Partial recurrence can enable robust and efficient computation

    , Communications AI and computing, Vol: 1, ISSN: 3091-292X

    Neural circuits are sparse and bidirectional. Meaning that signals flow from early sensory areas to later regions and back. Yet, between connected areas there exist some but not all pathways. How does this structure, somewhere between feedforward and fully recurrent, shape circuit function? To address this question, we designed a recurrent neural network model in which a set of weight matrices (i.e. pathways) can be combined to generate every network structure between feedforward and fully recurrent. We term these architectures partially recurrent neural networks (pRNNs). We trained over 25,000 pRNNs on a novel set of reinforcement learning tasks, designed to mimic multisensory navigation, and compared their performance across multiple functional metrics. Our findings reveal three key insights. First, in dense-cue environments, most pRNN architectures match or exceed the task performance, learning speed or robustness of fully recurrent networks, despite using as few as one quarter the number of parameters; in sparse-cue environments, many match but a substantial fraction underperform. These results demonstrate that partial recurrence can enable energy efficient, yet performant solutions. Second, each pathway’s functional impact is both task and circuit dependent. For instance, feedback connections enhance robustness to noise in some, but not all contexts. Third, different pRNN architectures learn solutions with distinct input sensitivities and memory dynamics, and these computational traits help to explain their functional capabilities. Overall, our results demonstrate that partial recurrence can enable robust and efficient computation- a finding that may help to explain why neural circuits are sparse and bidirectional, and shows how these principles can inform the design of artificial systems.
  • Journal article
    Frankel G, 2026,

    Design of a live-attenuated bacterial vaccine using effector network engineering

    , Nature Communications, ISSN: 2041-1723

    Enteropathogenic Escherichia coli (EPEC) and Citrobacter rodentium (CR) are extracellular enteric attaching and effacing (A/E) pathogens of humans and mice, respectively. Their virulence relies on intimate bacterial attachment and a network of type III secretion system effectors. Here, through systematic reduction and redesign of the effector network in CR, we develop an attenuated strain, CRV (CR Vaccine), encoding a subset of ten effectors. CRV colonises C57BL/6 mice ~100-fold lower than wild type CR (CRWT) without causing overt pathogenesis. Moreover, C3H/HeN mice, which succumb to CRWT infection, survive CRV challenge. Vaccination with CRV confers protection against subsequent CRWT infection in both mouse strains. Serological analysis reveals a repertoire of dominant CR antigens, including the O-antigen, the virulence factors intimin, EspA and Tir and the outer membrane proteins Lpp, OmpA, MetQ and CARC (an AIDA-like autotransporter). We show that CRWT and CRV immunisation elicits comparable B cell and antibody responses, which is contingent on intimate bacterial attachment. A corresponding EPEC strain (E. coli Vaccine, ECV) effectively colonises epithelial cells in a gut-on-chip model. These findings establish effector network minimisation as a generalisable strategy for rational bacterial attenuation and live-attenuated vaccine design.
  • Journal article
    Mostyn SN, Flores K, Hedger G, Nagaraj H, Rouse SL, Comstock LE, Bubeck Det al., 2026,

    Bacteroidales Secreted Antimicrobial Protein-1 receptor recognition is coupled to protease-activation to form bactericidal pores.

    , bioRxiv

    Bacteroidales secreted antimicrobial proteins (BSAPs) are diffusible MACPF-domain toxins that mediate intra-species antagonism in the gut microbiota. Here we define the mechanism of action of BSAP-1 from Bacteroides fragilis , showing how target specificity encoded within the N- and C-terminal domains is coordinated with pore-forming activity of the MACPF. We show that specificity of the toxin for its receptor is mediated by an extended interface comprised of the BSAP-1 C-terminal domain and residues on the receptor that differ from the orthologous protein of BSAP-1 producing strains. On the surface of susceptible cells, BSAP-1 undergoes proteolytic cleavage of an N-terminal regulatory domain, triggering its assembly into oligomeric pores. Cryo-electron microscopy of membrane-inserted BSAP-1 reveals a 13-subunit transmembrane β-barrel pore formed through canonical MACPF rearrangements. Comparative modelling supports a conserved oligomerization mechanism across the BSAP family despite diversification of receptor-binding domains that target either proteins or glycan receptors. Together, these findings establish BSAP-1 as a receptor-targeted, protease-activated antibacterial MACPF toxin and provide a framework for understanding how gut Bacteroidales spatially restrict toxin activation to shape strain-level competition.
  • Journal article
    Ferrando-Marco M, Berger S, Barkoulas M, 2026,

    Transcriptional feedback targeting Wnt pathway components reveals hidden heterogeneity in Caenorhabditis elegans seam cell lineages.

    , Genetics, Vol: 233

    Asymmetric cell division in the epidermal stem cells of Caenorhabditis elegans, known as seam cells, relies on the Wnt/β-catenin asymmetry pathway to generate daughter cells with distinct fates. However, whether components of this pathway are transcriptionally regulated during these divisions remains unclear. Here, we employ single-molecule fluorescence in situ hybridization to quantify mRNA distributions of key Wnt pathway components during L2 symmetric and asymmetric seam cell divisions. We find that transcripts encoding the negative regulators pry-1/Axin and apr-1/APC are enriched in posterior daughter cells, while those encoding the positive regulators sys-1/β-catenin, wrm-1/β-catenin, and lit-1/NLK, along with the transcription factor pop-1/TCF, are enriched in anterior daughter cells. Strikingly, molecular asymmetries are already evident following the L2 symmetric division, with anterior and posterior daughters exhibiting distinct levels of Wnt component expression and Wnt pathway activation. These mRNA distributions are surprising considering the established protein localizations that underpin the Wnt asymmetry model and suggest extensive postdivisional transcriptional regulation. We further demonstrate that pop-1 and pry-1 asymmetric expression partly depends on Wnt signaling activity. Investigation of protein distributions using knock-in reporters for PRY-1 and CAM-1 showed that protein accumulation patterns at L2 are consistent with transcript levels. Our findings uncover transcriptional feedback within the Wnt pathway that may reinforce robust fate specification and reveal molecular heterogeneity in seam cells with potential functional consequences for lineage behavior.
  • Journal article
    Zammit WH, Le Maistre LJ, Elliot TAE, Cain SA, Humphries MJ, Davis DM, Worboys JDet al., 2026,

    Inhibitory TIGIT signaling is dependent on T cell receptor activation.

    , Cell Rep, Vol: 45

    The immune checkpoint receptor T cell immunoreceptor with Ig and ITIM domains (TIGIT) can signal via cytoplasmic motifs to regulate T cell function. The signaling molecules that mediate inhibitory TIGIT signaling and its regulation in T cells remain poorly defined. Here, proximity proteomics is employed to define TIGIT-proximal proteins upon CD155 engagement, identifying several that are ligation-specific, including those involved in signaling (Grb2 and SOS1), cytoskeletal regulation (CD2AP and SdcBP), and endocytosis (IST1 and SNX3). Through crosslinking followed by immunoprecipitation, we show that TIGIT and CD2AP directly interact, representing a novel association. A TIGIT mutant (Y225A/Y231A) incapable of inhibitory signaling prevents recruitment of these proteins. Strikingly, T cell receptor (TCR) stimulation is essential for TIGIT to engage with these pathways. Mechanistically, phosphorylation of TIGIT requires both CD155 ligation and TCR activation, resulting in its signaling and internalization. TCR activation-dependent TIGIT signaling establishes a regulatory mechanism that limits checkpoint control to when functionally required.
  • Journal article
    Cheyne A, Oskoui EV, Broda A, Krishnan N, Liu Y, Robertson BD, Kaforou M, Larrouy-Maumus Get al., 2026,

    Metabolomics profiling reveals changes in peptidoglycan and redox metabolism between ancient and modern Mycobacterium tuberculosis

    , Microbiology Spectrum, Vol: 14, Pages: 1-15, ISSN: 2165-0497

    Mycobacterium tuberculosis (Mtb), the cause of tuberculosis, kills over one million people worldwide each year. Mtb is classified into ten distinct lineages, each harboring unique genetic changes that influence its survival, virulence, and transmissibility. Although metabolism plays a critical role in Mtb infection and persistence, the metabolomic profiles of different Mtb lineages remain poorly characterized. Here, by using metabolomic and bioinformatic approaches, we have determined the metabolome of representative strains belonging to three main lineages, namely lineage 1, lineage 2 and lineage 4. We show that the ancient lineage 1 has considerable differences in its metabolome compared to lineages 2 and 4. Those differences are mainly related to amino acids, peptidoglycan synthesis intermediates and ergothioneine, a sulphur-containing histidine derivative with potent antioxidant and redox properties. Taken together, these data represent the first comprehensive analysis of the metabolome of three main Mtb lineages.
  • Journal article
    Ferrando-Marco M, Lin S, Del Valle BG, Hintze M, Narunsky L, Huang J, Edwards S, Barkoulas Met al., 2026,

    HDAC1/2-mediated repression of Wnt receptor expression orients asymmetric division polarity in C. elegans.

    , Development

    Asymmetric cell division generates distinct daughter cells essential for tissue development, yet the mechanisms orienting division polarity within tissues remain incompletely understood. Here, we uncover a role for chromatin-mediated transcriptional repression in controlling polarity orientation during asymmetric division of C. elegans epidermal stem cells, known as the seam cells. Tissue-specific loss of the class I histone deacetylase hda-1, homologous to mammalian HDAC1/2, causes polarity reversals and reduces molecular asymmetry between daughter cells. Using Targeted DamID, we identify the Wnt receptors lin-17/Frizzled and cam-1/Ror as key targets. Single-molecule FISH reveals opposing expression gradients along the body axis, with cam-1 enriched anteriorly and lin-17 posteriorly. In hda-1 mutants, both receptors are upregulated and differences between seam cells are flattened. Overexpression of either receptor alone is sufficient to reproduce the polarity reversals, while co-overexpression produces additive effects. The polarity phenotype is independent of the canonical NuRD and SIN3 complexes, suggesting that HDA-1 acts through an alternative mechanism. These findings link histone deacetylase activity to Wnt receptor expression and suggest that graded receptor expression may provide cues that orient asymmetric division polarity.
  • Journal article
    Ishimoto N, He S, Smith TK, Frankel G, Beis Ket al., 2026,

    Phospholipid-1 independent biogenesis and function of the RP4 conjugation pilus

    , Nature Communications, Vol: 17, ISSN: 2041-1723

    Bacterial conjugation, the process of horizontal gene transfer between bacteria, is initiated by mating pair formation (MPF) via a conjugative pilus. Conjugation of the IncP RP4 plasmid is mediated by short mating pili. Here, we report the cryo-EM structure of the RP4 pilus at 2.74 Å resolution. Uniquely, both the structural and quantitative mass spectral analyses revealed that the cyclic TrbC pilin subunit is not lipidated. Consistently, an E. coli pgsA mutant lacking phosphatidylglycerol (PG) can serve as a donor of RP4 but not of F- (pKpQIL), H- (R27) or W- (R388) pili, whose biogenesis and DNA transfer is PG-dependent. RP4 is the first example of a lipid-independent functional mating pilus. This discovery suggests that an amphipathic lipid moiety is not universally essential for the biogenesis of conjugative pili and MPF, providing an alternative model for their assembly and function. These data expand our understanding of the diverse bacterial mechanisms employ to transfer genetic material.
  • Journal article
    Chapman ASA, Adanu SK, Dalin C, Devenish A, Griffiths GH, Robinson EJZ, Adolph B, Franks P, Gebrehiwot T, Mwitwa J, Seddon N, Tobias JA, Newbold Tet al., 2026,

    Assessing trade-off risk between crop production and vertebrate biodiversity in three African countries

    , People and Nature, Vol: 8, Pages: 2796-2814

    Governments worldwide are committed to eliminating hunger and conserving biodiversity, reflected in United Nations Sustainable Development Goals 2 (Zero Hunger) and 15 (Life on Land). Expanding agricultural lands to meet growing food demands often threatens biodiversity, creating potential trade-offs between these objectives. To understand the potential trade-off risks, we need to determine the extent to which croplands are located in areas that are also species-rich and which crops pose the greatest biodiversity risk. We identify areas where there is a trade-off risk between vertebrate biodiversity and crop production important for food and livelihoods across Ethiopia, Ghana, and Zambia. We evaluate trade-off risk via three metrics: (i) the footprint, mapping the overlap between crop production and ecological priority areas; (ii) two measures of trade-off risk based on the number of species potentially impacted: one measuring average local species richness affected per unit area used to grow a crop or crop group—domestic or traded (trade-off risk intensity), and a second measuring this average local species richness impacted but summed across the total area used to grow the crop/crop group (trade-off risk potential); and (iii) the hotspots where crops are grown in regions especially rich in vertebrates. Trade-off risk varies more among crop types and regions, and relatively little, on average, between crops grown for international trade versus crops grown primarily for domestic consumption. The crops with the greatest total risk potential are wheat in Ethiopia, cocoa in Ghana, and maize in Zambia. In all three countries, coffee poses the greatest trade-off risk intensity to threatened species and bananas exceed the expected trade-off risk intensity. Trade-off risks are context-dependent and optimal management will therefore be both country- and crop-specific. As there is not just one crop posing a consistently high risk of trade-off for biodiversity, and many

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