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  • Journal article
    Liu M, Prentice IC, Menviel L, Harrison SPet al., 2025,

    Correction to: Past rapid warmings as a constraint on greenhouse-gas climate feedbacks (Communications Earth & Environment, (2022), 3, 1, (196), 10.1038/s43247-022-00536-0)

    , Communications Earth and Environment, Vol: 6

    Correction to:Communications Earth & Environmenthttps://doi.org/10.1038/s43247-022-00536-0, published online 30 August 2022 In the version of this article originally published, three estimates of equilibrium climate sensitivity (ECS) derived from different sources were used to convert feedback strength into the unitless measure – gain – on the assumption that these were independent. In fact, these were not independent, and so combining them yields a too-narrow uncertainty range. The authors decided to only use the “very likely” (instead of “likely”) range from IPCC WG1 AR6 and treat it as a 90% confidence interval. Additionally, the gain is not normally distributed but is highly asymmetric, as it is the negative of the ratio of two approximately normally distributed variables, feedback strength (c) and the net feedback parameter (αnet), with a non-zero centre. There is no standard way to derive confidence intervals from standard error for such a variable. Therefore, in the correct version, only the standard error of the gain is provided, instead of giving confidence intervals. Besides, since calculating standard error by the error propagation rule requires the input variables to be at least approximately normally distributed, the gain was calculated directly from the net feedback parameter (αnet, which is assumed to be normally distributed) corresponding to ECS (which is not normally distributed). The changes implemented have no impact on the calculated feedback strengths, but they do have an impact on the estimated gains. Since confidence intervals are no longer provided for the gains, the comparison is focused on the feedback strengths. The authors would like to thank Dr. B. B. Cael from the National Oceanography Centre for bringing this issue to their attention with advice about the choice of ECS and how the very likely range should be interpreted into confidence interval. The manuscript has now been corrected i

  • Journal article
    Herzog MK-M, Peters A, Shayya N, Cazzaniga M, Kaka Bra K, Arora T, Barthel M, Gül E, Maurer L, Kiefer P, Christen P, Endhardt K, Vorholt JA, Frankel G, Heimesaat MM, Bereswill S, Gahan CGM, Claesson MJ, Domingo-Almenara X, Hardt W-Det al., 2025,

    Comparing Campylobacter jejuni to three other enteric pathogens in OligoMM12 mice reveals pathogen-specific host and microbiota responses.

    , Gut Microbes, Vol: 17

    Campylobacter jejuni, non-typhoidal Salmonella spp., Listeria monocytogenes and enteropathogenic/enterohemorrhagic Escherichia coli (EPEC/EHEC) are leading causes of food-borne illness worldwide. Citrobacter rodentium has been used to model EPEC and EHEC infection in mice. The gut microbiome is well-known to affect gut colonization and host responses to many food-borne pathogens. Recent progress has established gnotobiotic mice as valuable models to study how microbiota affect the enteric infections by S. Typhimurium, C. rodentium and L. monocytogenes. However, for C. jejuni, we are still lacking a suitable gnotobiotic mouse model. Moreover, the limited comparability of data across laboratories is often negatively affected by variations between different research facilities or murine microbiotas. In this study, we applied the standardized gnotobiotic OligoMM12 microbiota mouse model and compared the infections in the same facility. We provide evidence of robust colonization and significant pathological changes in OligoMM12 mice following infection with these pathogens. Moreover, we offer insights into pathogen-specific host responses and metabolite signatures, highlighting the advantages of a standardized mouse model for direct comparisons of factors influencing the pathogenesis of major food-borne pathogens. Notably, we reveal for the first time that C. jejuni stably colonizes OligoMM12 mice, triggering inflammation. Additionally, our comparative approach successfully identifies pathogen-specific responses, including the detection of genes uniquely associated with C. jejuni infection in humans. These findings underscore the potential of the OligoMM12 model as a versatile tool for advancing our understanding of food-borne pathogen interactions.

  • Journal article
    Moulick D, Santra SC, Majumdar A, Das A, Chowardhara B, Saha B, Ghosh D, Majumdar J, Upadhyay MK, Yadav P, Sarkar S, Garai S, Dhar A, Dey S, Mandal S, Choudhury S, Pattnaik BK, Dash GK, Repalli SK, Hossain Aet al., 2025,

    Efficacy of Seed Priming Technology in Ameliorating Metals and Metalloids Toxicity in Crops: Prospective and Issues

    , REVIEWS OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, Vol: 263, ISSN: 0179-5953
  • Journal article
    Youn T, Kim G, Hariharan P, Li X, Ahmed W, Byrne B, Liu X, Guan L, Chae PSet al., 2025,

    Improved Pendant-Bearing Glucose-Neopentyl Glycols for Membrane Protein Stability.

    , Bioconjug Chem

    Membrane proteins are biologically and pharmaceutically significant, and determining their 3D structures requires a membrane-mimetic system to maintain protein stability. Detergent micelles are widely used as membrane mimetics; however, their dynamic structures often lead to the denaturation and aggregation of encapsulated membrane proteins. To address the limitations of classical detergents in stabilizing membrane proteins, we previously reported a class of glucose-neopentyl glycols (GNGs) and their pendant-bearing versions (P-GNGs), several of which proved more effective than DDM in stabilizing membrane proteins. In this study, we synthesized additional GNG derivatives by varying the lengths of the pendant (P-GNGs), and by introducing hemifluorinated pendants to the GNG scaffold (fluorinated pendant-bearing GNGs or FP-GNGs). The synthetic flexibility of the GNG chemical architecture allowed us to create a diverse range of derivatives, essential for the effective optimization of detergent properties. When tested with two model membrane proteins (a transporter and a G-protein coupled receptor (GPCR)), most of the new (F)P-GNGs demonstrated superior stabilization of these membrane proteins compared to DDM, the original GNG (OGNG)), and a previously developed P-GNG (i.e., GNG-3,14). Notably, several P-GNGs synthesized in this study were as effective as or even better than lauryl maltose neopentyl glycol (LMNG) in stabilizing a human GPCR, beta2 adrenergic receptor (β2AR). Enhanced protein stability was particularly observed for the P-GNGs with a butyl (C4) or pentyl (C5) pendant, indicating that these pendant sizes are optimal for membrane protein stability. The volumes of these pendants appear to minimize the empty spaces in the micelle interiors, thereby enhancing detergent-detergent interactions in micelles complexed with the membrane proteins. Additionally, we identified one FP-GNG that was more efficient at extracting the transporter and more effective at st

  • Journal article
    Rice AJ, Sword TT, Chengan K, Mitchell DA, Mouncey NJ, Moore SJ, Bailey CBet al., 2025,

    Cell-free synthetic biology for natural product biosynthesis and discovery.

    , Chem Soc Rev

    Natural products have applications as biopharmaceuticals, agrochemicals, and other high-value chemicals. However, there are challenges in isolating natural products from their native producers (e.g. bacteria, fungi, plants). In many cases, synthetic chemistry or heterologous expression must be used to access these important molecules. The biosynthetic machinery to generate these compounds is found within biosynthetic gene clusters, primarily consisting of the enzymes that biosynthesise a range of natural product classes (including, but not limited to ribosomal and nonribosomal peptides, polyketides, and terpenoids). Cell-free synthetic biology has emerged in recent years as a bottom-up technology applied towards both prototyping pathways and producing molecules. Recently, it has been applied to natural products, both to characterise biosynthetic pathways and produce new metabolites. This review discusses the core biochemistry of cell-free synthetic biology applied to metabolite production and critiques its advantages and disadvantages compared to whole cell and/or chemical production routes. Specifically, we review the advances in cell-free biosynthesis of ribosomal peptides, analyse the rapid prototyping of natural product biosynthetic enzymes and pathways, highlight advances in novel antimicrobial discovery, and discuss the rising use of cell-free technologies in industrial biotechnology and synthetic biology.

  • Journal article
    Sadaf A, Yun HS, Lee H, Stanfield S, Lan B, Salomon K, Woubshete M, Kim S, Ehsan M, Bae H, Byrne B, Loland CJ, Liu X, Guan L, Im W, Chae PSet al., 2025,

    Multiple Pendants-Bearing Triglucosides for Membrane Protein Studies: Effects of Pendant Length and Number on Micelle Interior Hydration and Protein Stability.

    , Biomacromolecules

    Membrane proteins play central roles in cell physiology and are the targets of over 50% of FDA-approved drugs. In the present study, we prepared single alkyl-chained triglucosides decorated with multiple pendants, designated multiple pendant-bearing glucosides (MPGs), to enhance membrane protein stability. The new detergents feature two and four pendants of varying size at the hydrophilic-lipophilic interfaces, designated MPG-Ds and MPG-Ts, respectively. When tested with model membrane proteins, including the human adrenergic receptor (β2AR), the tetra-pendant-bearing MPGs (MPG-Ts) demonstrated superior performance compared to the dipendant analogs (MPG-Ds) and the gold standard DDM. All-atom molecular dynamics (MD) simulations results reveal that the four-pendant configuration of this detergent is remarkably effective in excluding water from the hydrophobic micelle interiors compared to the dipendant MPGs and DDM, an unprecedented feature of this new detergent. Our findings provide a novel strategy for designing water-resistant detergents, advancing the field of membrane protein research.

  • Journal article
    Dodds IL, Watts EC, Schuster M, Buscaill P, Tumas Y, Holton NJ, Song S, Stuttmann J, Joosten MHAJ, Bozkurt T, van der Hoorn RALet al., 2025,

    Immunity gene silencing increases transient protein expression in Nicotiana benthamiana.

    , Plant Biotechnol J
  • Journal article
    Franks NP, Wisden W, 2025,

    Reply to: A curious concept of CNS clearance.

    , Nat Neurosci
  • Journal article
    Mengoli G, Sandy P H, Prentice IC, 2025,

    The Response of Carbon Uptake to Soil Moisture Stress:Adaptation to Climatic Aridity

    , Global Change Biology, ISSN: 1354-1013
  • Journal article
    Negi P, Pandey M, Paladi RK, Majumdar A, Pandey SP, Barvkar VT, Devarumath R, Srivastava AKet al., 2025,

    Stomata-Photosynthesis Synergy Mediates Combined Heat and Salt Stress Tolerance in Sugarcane Mutant M4209.

    , Plant Cell Environ

    Sugarcane (Saccharum officinarum L.) is an economically important long-duration crop which is currently facing concurrent heat waves and soil salinity. The present study evaluates an inducible salt-tolerant sugarcane mutant M4209, developed via radiation-induced mutagenesis of elite check variety Co 86032, under heat (42/30°C; day/night), NaCl (200 mM) or heat + NaCl (HS)-stress conditions. Though heat application significantly improved plant growth and biomass in both genotypes, this beneficial impact was partially diminished in Co 86032 under HS-stress conditions, coinciding with higher Na+ accumulation and lower triacylglycerol levels. Besides, heat broadly equalised the negative impact on NaCl stress in terms of various physiological and biochemical attributes in both the genotypes, indicating its spaciotemporal advantage. The simultaneous up- and downregulation of antagonistic regulators, epidermal patterning factor (EPF) 9 (SoEPF9) and SoEPF2, respectively attributed to the OSD (Open Small Dense) stomatal phenotype in M4209, which resulted into enhanced conductance, transpirational cooling and gaseous influx. This led to improved photoassimilation, which was supported by higher plastidic:nonplastidic lipid ratio, upregulation of SoRCA (Rubisco activase) and better source strength, resulting in overall plant growth enhancement across all the tested stress scenarios. Taken together, the present study emphasised the knowledge-driven harnessing of stomatal-photosynthetic synergy for ensuring global sugarcane productivity, especially under "salt-heat" coupled stress scenarios.

  • Journal article
    Farah A, Patel R, Poplawski P, Wastie BJ, Tseng M, Barry AM, Daifallah O, Dubb A, Paul I, Cheng HL, Feroz F, Su Y, Chan M, Zeilhofer HU, Price TJ, Bennett DL, Bannister K, Dawes JMet al., 2025,

    A role for leucine-rich, glioma inactivated 1 in regulating pain sensitivity

    , Brain, Vol: 148, Pages: 1001-1014, ISSN: 0006-8950

    <jats:title>Abstract</jats:title> <jats:p>Neuronal hyperexcitability is a key driver of persistent pain states, including neuropathic pain. Leucine-rich, glioma inactivated 1 (LGI1) is a secreted protein known to regulate excitability within the nervous system and is the target of autoantibodies from neuropathic pain patients. Therapies that block or reduce antibody levels are effective at relieving pain in these patients, suggesting that LGI1 has an important role in clinical pain.</jats:p> <jats:p>Here we have investigated the role of LGI1 in regulating neuronal excitability and pain-related sensitivity by studying the consequences of genetic ablation in specific neuron populations using transgenic mouse models.</jats:p> <jats:p>LGI1 has been well studied at the level of the brain, but its actions in the spinal cord and peripheral nervous system are poorly understood. We show that LGI1 is highly expressed in dorsal root ganglion (DRG) and spinal cord dorsal horn neurons in both mouse and human. Using transgenic mouse models, we genetically ablated LGI1, either specifically in nociceptors (LGI1fl/Nav1.8+) or in both DRG and spinal neurons (LGI1fl/Hoxb8+). On acute pain assays, we found that loss of LGI1 resulted in mild thermal and mechanical pain-related hypersensitivity when compared with littermate controls. In LGI1fl/Hoxb8+ mice, we found loss of Kv1 currents and hyperexcitability of DRG neurons. LGI1fl/Hoxb8+ mice displayed a significant increase in nocifensive behaviours in the second phase of the formalin test (not observed in LGI1fl/Nav1.8+ mice), and extracellular recordings in LGI1fl/Hoxb8+ mice revealed hyperexcitability in spinal dorsal horn neurons, including enhanced wind-up. Using the spared nerve injury model, we found that LGI1 expression was dysregulated in the spinal cord. LGI1fl/Nav1.8+ mice showed no differences in nerve injury-induced mechanical hypersensitivit

  • Journal article
    Allen ME, Sun Y, Chan CL, Paez-Perez M, Ces O, Elani Y, Contini Cet al., 2025,

    Thermally Driven Dynamic Behaviors in Polymeric Vesicles.

    , Small

    Stimuli-responsive polymeric vesicles offer a versatile platform for mimicking dynamic cell-like behaviors for synthetic cell applications. In this study, thermally responsive polymeric droplets derived from poly(ethylene oxide)-poly(butylene oxide) (PEO-PBO) polymersomes, aiming to create synthetic cell models that mimic key biological functions are developed. Upon heating, the nanoscale vesicles undergo fusion, transforming into sponge-like microscale droplets enriched with membrane features. By modulating the temperature, these droplets display dynamic properties such as contractility, temperature-induced fusion, and cargo trapping, including small molecules and bacteria, thereby demonstrating their ability to dynamically interface with biological entities. The findings demonstrate the potential of our sponge-like droplets in synthetic cell applications, contributing to the understanding of PEO-PBO polymersomes' unique characteristics, expanding the capabilities of synthetic cell structures, and representing an exciting possibility for advancing soft matter engineering to cell-like behaviors.

  • Journal article
    Ferrando-Marco M, Barkoulas M, 2025,

    EFL-3/E2F7 modulates Wnt signalling by repressing the Nemo-like kinase LIT-1 during asymmetric epidermal cell division in Caenorhabditis elegans.

    , Development, Vol: 152

    The E2F family of transcription factors is conserved in higher eukaryotes and plays pivotal roles in controlling gene expression during the cell cycle. Most canonical E2Fs associate with members of the Dimerisation Partner (DP) family to activate or repress target genes. However, atypical repressors, such as E2F7 and E2F8, lack DP interaction domains and their functions are less understood. We report here that EFL-3, the E2F7 homologue of Caenorhabditis elegans, regulates epidermal stem cell differentiation. We show that phenotypic defects in efl-3 mutants depend on the Nemo-like kinase LIT-1. EFL-3 represses lit-1 expression through direct binding to a lit-1 intronic element. Increased LIT-1 expression in efl-3 mutants reduces POP-1/TCF nuclear distribution, and consequently alters Wnt pathway activation. Our findings provide a mechanistic link between an atypical E2F family member and NLK during C. elegans asymmetric cell division, which may be conserved in other animals.

  • Journal article
    Stark KA, Clegg T, Bernhardt JR, Grainger TN, Kempes CP, Savage V, O'Connor MI, Pawar Set al., 2025,

    Toward a More Dynamic Metabolic Theory of Ecology to Predict Climate Change Effects on Biological Systems.

    , Am Nat, Vol: 205, Pages: 285-305

    AbstractThe metabolic theory of ecology (MTE) aims to link biophysical constraints on individual metabolic rates to the emergence of patterns at the population and ecosystem scales. Because MTE links temperature's kinetic effects on individual metabolism to ecological processes at higher levels of organization, it holds great potential to mechanistically predict how complex ecological systems respond to warming and increased temperature fluctuations under climate change. To scale up from individuals to ecosystems, applications of classical MTE implicitly assume that focusing on steady-state dynamics and averaging temperature responses across individuals and populations adequately capture the dominant attributes of biological systems. However, in the context of climate change, frequent perturbations from steady state and rapid changes in thermal performance curves via plasticity and evolution are almost guaranteed. Here, we explain how some of the assumptions made when applying MTE's simplest canonical expression can lead to blind spots in understanding how temperature change affects biological systems and how this presents an opportunity for formal expansion of the theory. We review existing advances in this direction and provide a decision tree for identifying when dynamic modifications to classical MTE are needed for certain research questions. We conclude with empirical and theoretical challenges to be addressed in a more dynamic MTE for understanding biological change in an increasingly uncertain world.

  • Journal article
    Chen T, Hojka M, Davey P, Sun Y, Zhou F, Lawson T, Nixon PJ, Lin Y, Liu Let al., 2025,

    Engineering Rubisco condensation in chloroplasts to manipulate plant photosynthesis

    , Plant Biotechnology Journal, ISSN: 1467-7644
  • Journal article
    Fieldwalker A, Patel R, Zhao L, Kucharczyk MW, Mansfield M, Bannister Ket al., 2025,

    A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms.

    , Eur J Pain, Vol: 29

    BACKGROUND: Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation. METHODS: Perceptual (quantitative sensory testing) and spinal neuronal (in vivo electrophysiology) assessment was performed in healthy humans and rats respectively upon application of parallel CPM/diffuse noxious inhibitory controls (cuff algometry) and TSP/wind-up (pinprick) paradigms alongside pupillometry. RESULTS: In humans, repetitive pinprick stimulation produced TSP while concurrent application of a noxious conditioning stimulus did not affect pain ratings to a single pinprick stimulus, repetitive stimulation or the wind-up ratio. In rats, repetitive pinprick produced neuronal wind-up while concurrent application of a noxious conditioning stimulus inhibited neuronal responses to a single stimulus and repetitive stimulation but not the wind-up ratio. For pupillometry experiments, dilatory responses did not increase during application of a TSP or CPM paradigm in humans, while reliable rat responses were not obtained. CONCLUSIONS: Under the conditions of our study, spinal amplification mechanisms surpassed descending inhibitory controls while pupillometry did not offer a reliable indicator of endogenous pain modulatory mechanism function. SIGNIFICANCE: In this translational healthy human an

  • Journal article
    Yu C, Zheng J, Zhang Y, Hu Y, Luo W, Zhang J, Yu J, Liu J, Nixon PJ, Zhou W, Shao Set al., 2025,

    Towards sustainable spirulina farming: Enhancing productivity and biosafety with a salinity-biostimulants strategy.

    , Bioresour Technol, Vol: 419

    Arthrospira platensis (spirulina) is pivotal to the global microalgae industry, valued for its nutritional and bioactive properties. However, its sustainable production is challenged by freshwater scarcity and biological contaminants. This study introduces a salinity-biostimulants strategy to adapt a freshwater spirulina strain, CBD05, to near-seawater salinity (3 %). Exogenous glycine betaine (GB) and nitric oxide (NO), typical salinity enhancers, improved biomass productivity (0.36 g L-1 d-1), C-phycocyanin (C-PC) yield (83 mg L-1 d-1), and the economic output-to-input ratio was significantly enhanced. Metabolomic analysis linked salt tolerance to elevated amino acid accumulation, protein synthesis, and glycolysis, while transcriptional evidence highlighted enhanced carbon fixation and nitrogen assimilation towards C-PC synthesis upon addition of GB and NO. This strategy also demonstrated high resistance to Microcystis aeruginosa, a common contaminant in open systems. It provides a sustainable and cost-effective approach for industry-oriented spirulina production in freshwater-limited regions.

  • Thesis dissertation
    Sabey D, 2025,

    Characterising Nucleolar Architecture in Trypanosoma brucei

  • Journal article
    Benjamin SV, Taylor ME, Drickamer K, 2025,

    Application of a human lectin array to rapid in vitro screening of sugar-based epitopes that can be used as targeting tags for therapeutics.

    , Glycobiology, Vol: 35

    An increasing number of clinical applications employ oligosaccharides as tags to direct therapeutic proteins and RNA molecules to specific target cells. Current applications are focused on endocytic receptors that result in cellular uptake, but additional applications of sugar-based targeting in signaling and protein degradation are emerging. These approaches all require development of ligands that bind selectively to specific sugar-binding receptors, known as lectins. In the work reported here, a human lectin array has been employed as a predictor of targeting selectivity of different oligosaccharide ligands and as a rapid in vitro screen to identify candidate targeting ligands. The approach has been validated with existing targeting ligands, such as a synthetic glycomimetic GalNAc cluster ligand that targets siRNA molecules to hepatocytes through the asialoglycoprotein receptor. Additional small oligosaccharides that could selectively target other classes of cells have also been identified and the potential of larger glycans derived from glycoproteins has been investigated. In initial screens, potential ligands for targeting either vascular or sinusoidal endothelial cells and plasmacytoid dendritic cells have been identified. Lectin array screening has also been used to characterize the selectivity of glycolipid-containing liposomes that are used as carriers for targeted delivery. The availability of a rapid in vitro screening approach to characterizing natural oligosaccharides and glycomimetic compounds has the potential to facilitate selection of appropriate targeting tags before undertaking more complex in vivo studies such as measuring clearance in animals.

  • Journal article
    Brown CP, Armstrong A, Mann DJ, 2025,

    Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay.

    , J Vis Exp

    Compounds that form covalent bonds with specific target proteins offer a variety of advantages as chemical probes and therapeutic agents. Most commonly, mildly reactive, electrophilic small molecules are employed to form covalent bonds with select cysteine side chains in specific proteins. Electrophile-first approaches of ligand discovery, whereby a library of electrophilic small molecules are screened against a protein target, have become popular as they avoid the need for time-consuming downstream installation of an electrophilic warhead. Such screening is complicated, however, as electrophilic ligands can exhibit a wide range of different rates of spontaneous reaction with cysteines. Quantitative-irreversible tethering (qIT) offers a fluorescence-based method for hit identification and development that normalizes data for these differences in intrinsic compound reactivity. Rates of reaction of individual compounds with a target protein are determined and compared to compound reactivity with the unstructured tripeptide glutathione (this being a proxy for spontaneous compound reaction), enabling the identification of compounds that preferentially react with the protein of interest. This methodology has been successfully applied to identify selective covalent fragments against several drug targets, including SARS-CoV-2 main protease, cyclin-dependent kinase 2, and RAP27A. Here, we demonstrate the application of qIT to a target protein to generate a quantitative and robust data set, allowing prioritization of hit ligands for future development.

  • Journal article
    Potapova N, Whitford H, Hodge J, Price Eet al., 2025,

    Optimal Weight Loss of Pink Pigeon (Nesoenas mayeri) Eggs During Incubation

    , Zoo Biology, ISSN: 0733-3188
  • Journal article
    Bell T, 2025,

    Replicating community dynamics reveals how initial composition shapes the functional outcomes of bacterial communities

    , Nature Communications, ISSN: 2041-1723
  • Journal article
    Katalinić J, Richards M, Auyang A, Millett JH, Kogenaru M, Windbichler Net al., 2025,

    Do the Shuffle: Expanding the Synthetic Biology Toolkit for Shufflon-like Recombination Systems.

    , ACS Synth Biol, Vol: 14, Pages: 363-372

    Naturally occurring DNA inversion systems play an important role in the generation of genetic variation and adaptation in prokaryotes. Shufflon invertase (SI) Rci from plasmid R64, recognizing asymmetric sfx sites, has been adopted as a tool for synthetic biology. However, the availability of a single enzyme with moderate rates of recombination has hampered the more widespread use of SIs. We identified 14 previously untested SI genes and their sfx sites in public databases. We established an assay based on single-molecule sequencing that allows the quantification of the inversion rates of these enzymes and determined cross-recognition to identify orthogonal SI/sfx pairs. We describe SI enzymes with substantially improved shuffling rates when expressed in an inducible manner in E. coli. Our findings will facilitate the use of SIs in engineering biology where synthetic shufflons enable the generation of millions of sequence variants in vivo for applications such as barcoding or experimental selection.

  • Journal article
    Lau EYX, Hodge JA, Rio JP, Pan T, Mannion PD, Turvey STet al., 2025,

    Using local ecological knowledge to identify land-use threats to the last wild population of the Chinese alligator <i>Alligator sinensis</i>

    , Oryx, Pages: 1-10, ISSN: 0030-6053

    <jats:title>Abstract</jats:title> <jats:p>Conservation management in human-modified landscapes requires information on the sustainability of interactions between people and biodiversity. Wild Chinese alligators <jats:italic>Alligator sinensis</jats:italic> only persist within the National Chinese Alligator Reserve in south-eastern China, where they live alongside agricultural communities that utilize local terrestrial and wetland habitats. We conducted an interview survey of communities within and around the Reserve to evaluate whether local ecological knowledge can provide a baseline on the species' local status and trends, and to understand the relationships between land-use practices and alligator presence and survival. Respondents within the Reserve were more likely to recognize alligators, report sightings and perceive declines than other respondents. Absolute levels of knowledge and experience of alligators were low, highlighting the species' perilous status, and analysis of correlative patterns between respondents' experiences and associated data on human–environmental interactions provides new conservation-relevant insights. Alligator sightings were more likely to be reported by respondents who did not grow crops, and eggs and nests by those who did not utilize local water sources for irrigation, suggesting that existing environmental pressures associated with agriculture may be unsustainable for alligators. Although respondents who lived outside the Reserve were more likely to use agrochemicals, we found no relationship between pesticide or fertilizer usage and variation in respondent awareness or experience of alligators. Our findings indicate that China's last wild alligators continue to experience negative human pressures, and current land-use practices are probably incompatible with long-term alligator survival.</jats:p>

  • Journal article
    ZHOU B, Cai W, Zhu Z, Wang H, Harrison SP, Prentice ICet al., 2025,

    A general model for the seasonal to decadal dynamics of leaf area

    , Global Change Biology, ISSN: 1354-1013
  • Journal article
    Sabelleck B, Deb S, Levecque SCJ, Freh M, Reinstädler A, Spanu PD, Thordal-Christensen H, Panstruga Ret al., 2025,

    A powdery mildew core effector protein targets the host endosome tethering complexes HOPS and CORVET in barley.

    , Plant Physiol

    Powdery mildew fungi are serious pathogens affecting many plant species. Their genomes encode extensive repertoires of secreted effector proteins that suppress host immunity. Here, we revised and analyzed the candidate secreted effector protein (CSEP) effectome of the powdery mildew fungus, Blumeria hordei (Bh). We identified seven putative effectors that are broadly conserved in powdery mildew species, suggesting that they are core effectors of these phytopathogens. We showed that one of these effectors, CSEP0214, interacts with the barley (Hordeum vulgare) vacuolar protein sorting 18 (VPS18) protein, a shared component of the class C core vacuole/endosome tethering (CORVET) and homotypic fusion and protein-sorting (HOPS) endosomal tethering complexes that mediate fusion of early endosomes and multivesicular bodies, respectively, with the central vacuole. Overexpression of CSEP0214 and knockdown of either VPS18, HOPS-specific VPS41 or CORVET-specific VPS8 blocked the vacuolar pathway and the accumulation of the fluorescent vacuolar marker protein (SP)-RFP-AFVY in the endoplasmic reticulum. Moreover, CSEP0214 inhibited the interaction between VPS18 and VPS16, which are both shared components of CORVET as well as HOPS. Additionally, introducing CSEP0214 into barley leaf cells blocked the hypersensitive cell death response associated with resistance gene-mediated immunity, indicating that endomembrane trafficking is required for this process. CSEP0214 expression also prevented callose deposition in cell wall appositions at attack sites and encasements of fungal infection structures. Our results indicate that the powdery mildew core effector CSEP0214 is an essential suppressor of plant immunity.

  • Journal article
    Rey C, Jones K, Stacey K, Evans A, Worboys J, Howell G, Sheppard S, Davis MBE FMedSci Det al., 2025,

    CD8α and CD70 mark human natural killer cell populations which differ in cytotoxicity

    , Frontiers in Immunology, ISSN: 1664-3224
  • Journal article
    Benjamin SV, Taylor ME, Drickamer K, 2025,

    Application of a human lectin array to rapid<i>in vitro</i>screening of sugars used as targeting tags for therapeutics

    <jats:title>Abstract</jats:title><jats:p>An increasing number of clinical applications employ oligosaccharides as tags to direct therapeutic proteins and RNA molecules to specific target cells. Current applications are focused on endocytic receptors that result in cellular uptake, but additional applications of sugar-based targeting in signaling and protein degradation are emerging. These approaches all require development of ligands that bind selectively to specific sugar-binding receptors, known as lectins. In the work reported here, a human lectin array has been employed as a predictor of targeting specificity of different oligosaccharide ligands and as a rapid<jats:italic>in vitro</jats:italic>screen to identify candidate targeting ligands. The approach has been validated with existing targeting ligands, such as a GalNAc cluster ligand that targets siRNA molecules to hepatocytes through the asialoglycoprotein receptor. Additional small oligosaccharides that can selectively target other classes of cells have also been identified and the potential of larger glycans derived from glycoproteins has been investigated. In initial screens, ligands for targeting either vascular or sinusoidal endothelial cells and plasmacytoid dendritic cells have been identified. Lectin array screening has also been used to characterize the specificity of glycolipid-containing liposomes that are used as carriers for targeted delivery. The availability of a rapid<jats:italic>in vitro</jats:italic>screening approach to characterizing natural oligosaccharides and glycomimetic compounds has the potential to facilitate selection of appropriate targeting tags before undertaking more complex<jats:italic>in vivo</jats:italic>studies.</jats:p>

  • Journal article
    Willis K, Burt A, 2025,

    Engineering drive-selection balance for localized population suppression with neutral dynamics.

    , Proc Natl Acad Sci U S A, Vol: 122

    While the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for many species due to the males disappearing after a single generation, necessitating large, repeated releases to maintain sufficient impact. Synthetic gene drives promise more efficient approaches since they can increase in frequency from rare, yet this also allows them to spread across a landscape, which may not always be desired. Between these two extremes are selectively neutral genetic constructs which persist at the frequency they are released, offering the potential for efficient suppression that remains localized. One way to achieve this would be to have perfect balance, at all construct frequencies, between gene drive increasing frequency and selection decreasing it. Here, we describe a way to closely approximate this balance using a toxin-antidote genetic construct that causes recessive lethality or sterility, encodes a genomic editor that makes dominant lethal or sterile edits in the genome, and provides protection against the action or consequences of the editing. Computer modeling shows that this design can be 100-fold more efficient than sterile males, increasing to 1,000-fold when released alongside a genetic booster. We describe designs for CRISPR-based molecular construction, including options that avoid using recoded genes as antidotes.

  • Journal article
    Ren Y, Wang H, Harrison SP, Prentice IC, Mengoli G, Zhao L, Reich PB, Yang Ket al., 2025,

    Incorporating the acclimation of photosynthesis and leaf respiration in the Noah-MP land surface model: model development and evaluation

    , Journal of Advances in Modeling Earth Systems, ISSN: 1942-2466

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