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PosterBoi S, Mathias S, Huang Y-H, et al., 2025,
Optimizing rep proteins expression balance for enhanced production of recombinant AAV vectors
, European Society of Cell and Gene TherapyRecombinant adeno-associated viruses (rAAV) are the main viral vectors used in clinical trials and are generally produced using transiently transfected HEK293 cells. A crucial aspect of optimizing rAAV production involves developing genetic constructs and methodologies tailored to maximize functional titers in these cell lines. Previous data from our group highlighted the significant impact of the interaction between specific HEK cell lines and AAV plasmids on titer yields. Therefore, understanding the mechanistic effects of Rep protein expression is essential. We conducted a detailed analysis of the Rep wildtype system to understand baseline expression levels, the dynamics of Rep protein ratios, and the separation of Rep from Cap proteins. Utilizing Western Blot and mRNA ddPCR techniques, we characterized the expression profiles of the four Rep proteins across various setups, including wildtype, split construct, and co-transfection, correlating these with viral genomes (vg), capsid particles (cp), and transduction units (TU) yields. This enabled us to formulate a hypothesis for optimal Rep expression strategies. Additionally, luciferase assays and tests with diverse transcriptional activities from established and novel promoters, beside varied Rep ratios, enriched our expression analysis. Our findings led to the development of a model for an optimal long Rep (lRep) to short Rep (sRep) ratio, allowing us to rescue combinations that initially resulted in low rAAV titers. In conclusion, we simplified the regulatory feedback loops of Rep expression by identifying optimal baseline levels for specific long-Rep and short-Rep isoforms, thereby enhancing the efficiency of rAAV production processes. Notably, the wildtype results contrasted with rAAV data, underscoring the intricate nature of the rAAV replication mechanism.
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Journal articleHain S, Fu MS, Wigg L, et al., 2025,
Brain-infiltrating CD4 T cells drive inflammatory microglia proliferation during cryptococcal meningitis in mice
, NATURE COMMUNICATIONS, Vol: 16 -
Journal articleZhao J, ZHOU B, Harrison SP, et al., 2025,
Eco-evolutionary modelling of global vegetation dynamics and the impact of CO2 during the late quaternary: insights from contrasting periods
, Earth System Dynamics, Vol: 16, Pages: 1655-1669, ISSN: 2190-4979Changes in climate have had major impacts on global vegetation during the Quaternary. However, variations in CO2 levels also play a role in shaping vegetation dynamics by influencing plant productivity and water-use efficiency and consequently the relative competitive success of the C3 and C4 photosynthetic pathways. We use an eco-evolutionary optimality (EEO)-based modelling approach to examine the impacts of climate fluctuations and CO2-induced alterations on gross primary production (GPP). We considered two contrasting periods, the Last Glacial Maximum (LGM; 21 000 years before present) and the mid-Holocene (MH; 6000 years before present) and compared both to pre-industrial (PI) conditions. The LGM, characterized by generally colder and drier climate, had a CO2 level close to the minimum for effective C3 plant operation. In contrast, the MH had warmer summers and increased monsoonal rainfall in the Northern Hemisphere, although with a CO2 level still below the PI. We simulated vegetation primary production at the LGM and the MH compared to the PI baseline using a light-use efficiency model that simulates GPP coupled to an EEO model that simulates leaf area index (LAI) and C3 C4 competition. We found that low CO2 at the LGM was nearly as important as climate in reducing tree cover, increasing the abundance of C4 plants and lowering GPP. Global GPP in the MH was similar to the PI (although greater than the LGM), also reflecting CO2 constraints on plant growth despite the positive impacts of warmer and/or wetter climates experienced in the Northern Hemisphere and tropical regions. These results emphasize the importance of taking account of impacts of changing CO2 levels on plant growth to model ecosystem changes.
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Journal articleMitchell Z, Den Hoed J, Claassen W, et al., 2025,
The NuRD component CHD3 promotes BMP signalling during cranial neural crest cell specification
, EMBO Reports, Vol: 26, Pages: 4723-4741, ISSN: 1469-221XPathogenic genetic variants in the NuRD component CHD3 cause Snijders Blok–Campeau Syndrome, a neurodevelopmental disorder manifesting with intellectual disability and craniofacial anomalies. To investigate the role of CHD3 in craniofacial development, we differentiated control and CHD3-depleted human-induced pluripotent stem cells into cranial neural crest cells (CNCCs). In control lines, CHD3 is upregulated in early stages of CNCC specification, where it enhances the BMP signalling response by opening chromatin at BMP-responsive cis-regulatory elements and by increasing expression of BMP-responsive transcription factors, including DLX paralogs. CHD3 loss leads to repression of BMP target genes and loss of chromatin accessibility at cis-regulatory elements usually bound by BMP-responsive factors, causing an imbalance between BMP and Wnt signalling. Consequently, the CNCC specification fails, replaced by aberrant early-mesoderm identity, which can be partially rescued by titrating Wnt levels. Our findings highlight a novel role for CHD3 as a pivotal regulator of BMP signalling, essential for proper neural crest specification and craniofacial development. Moreover, these results suggest a molecular mechanism for the craniofacial anomalies of Snijders Blok–Campeau Syndrome.
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Journal articleStadinski BD, Mills EA, Humphries PA, et al., 2025,
Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire
, NATURE IMMUNOLOGY, ISSN: 1529-2908- Cite
- Citations: 1
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Journal articleAnuncibay Soto B, Ma Y, Nollet M, et al., 2025,
The locus coeruleus maintains core body temperature and protects against hypothermia during dexmedetomidine-induced sedation
, Proceedings of the National Academy of Sciences of USA, ISSN: 0027-8424 -
Journal articleWong J, Sanchez Garrido J, Rattle J, et al., 2025,
citrOgen: a synthesis-free polysaccharide and protein antigen-presentation to antibody-induction platform
, Nature Communications, Vol: 16, ISSN: 2041-1723Existing technologies employed to generate antibodies against bacterial polysaccharides and proteins rely on the availability of purified or synthetic antigens. Here, we present a genetics-based platform that utilises Citrobacter rodentium (CR), an enteric mouse pathogen, to both produce and present complex heterologous polysaccharides and protein antigen complexes during natural infection. As proof of concept, we use lipopolysaccharides (O), capsular polysaccharides (K) and type 3 fimbrial (T3F) antigens expressed by the WHO critical priority pathogens Klebsiella pneumoniae (KP) and Escherichia coli (EC). Following one infection cycle (28 days), CR induces specific IgG antibodies against KPO1, ECO25b, KPK2 and KPT3F. We demonstrate that the antibodies are functional in downstream applications, including protection against pathogenic KP challenge, KP capsular serotyping and KP biofilm inhibition. Whilst KP and EC antigens were used as prototypical examples, this modular platform is now readily adaptable to generate antibodies against diverse polysaccharide and protein antigens, with basic science, public health and therapeutic applications.
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Journal articleHarrison SP, Bartlein PJ, Cruz-Silva E, et al., 2025,
Paleoclimate Perspectives on Contemporary Climate Change
, ANNUAL REVIEW OF ENVIRONMENT AND RESOURCES, Vol: 50, Pages: 67-95, ISSN: 1543-5938 -
Journal articleWong J, Refaat A, Villacampa-Teixeira P, et al., 2025,
The assembly of a hybrid type IV secretion system by a Crohn’s disease associated Escherichia coli strain
, Nature Communications, Vol: 16, ISSN: 2041-1723Type IV secretion systems (T4SSs) are central to bacterial pathogenesis. Traditionally known for facilitating DNA transfer via conjugation, T4SSs also mediate biofilm formation. These biofilms are critical for the fitness of adherent-invasive Escherichia coli (AIEC), which are commonly isolated from Crohn’s disease patients and are known for propelling gut inflammation. Many AIEC strains carry F-like plasmids encoding the IncF subgroup of T4SSs. Unlike minimized systems with 12 core components, the IncF family is an expanded T4SS with additional genes that enhance conjugation. Here, we show that a biofilm-forming AIEC strain harbors an unusual IncF plasmid that lacks two conserved components essential for T4SS functionality. This strain forms a natural hybrid T4SS where the missing components are supplied by a co-residing chromosomal T4SS on an integrative and conjugative element (ICE). Biochemical assays reveal that this hybrid T4SS drives pilin polymerization and biofilm formation on epithelial cells. Furthermore, we show that a bacterial subpopulation expresses the IncF and ICE-encoded genes in response to host cells, leading to the assembly of biofilms and enhanced fitness in the gut. These findings uncover crosstalk between two evolutionary distant mobile genetic elements to form a hybrid T4SS that mediates biofilm biogenesis by a Crohn’s disease-associated pathogen.
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Journal articleSharrocks KL, Fanelli F, Liu Y, et al., 2025,
Stabilized D2R G protein-coupled receptor oligomers identify multi-state β-arrestin complexes
, Nature Communications, Vol: 16, ISSN: 2041-1723The G protein-coupled receptor (GPCR) superfamily directs central roles in many physiological and pathophysiological processes via diverse and complex mechanisms. GPCRs can exhibit signal pleiotropy via formation of di/oligomers both with themselves and other GPCRs. A deeper understanding of the molecular basis and functional role of oligomerization would facilitate rational design of activity-selective ligands. A structural model of the D2 dopamine receptor (D2R) homomer identified distinct combinations of substitutions likely to stabilize protomer interactions. Molecular modelling of β-arrestin-2 (βarr2) bound to predicted dimer models suggests a 2:2 receptor: βarr2 stoichiometry, with the dimer favouring βarr2 over Gαi coupling. A combination of biochemical, biophysical and super-resolution, single molecule imaging approaches demonstrated that the D2R mutant homomers exhibited greater stability. The mutant D2R homomers also exhibited bias towards recruitment of the GPCR adaptor protein βarr2 with either faster or ligand-independent βarr2 recruitment, increased internalization and reprogrammed regulation of ERK signaling. Through GPCR dimer-stabilization, we propose that D2R di/oligomerization has a role in βarr2-biased signaling.
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Journal articleDing R, Nobrega R, Prentice C, 2025,
Global assessment of environmental and plant-trait influences on root:shoot biomass ratios
, Global Change Biology, Vol: 31, ISSN: 1354-1013The distribution of assimilated carbon (C) among roots, stems, and leaves is a central process in terrestrial ecosystem dynamics. Yet the biomass allocation schemes used in current global vegetation and land surface models pre-date the existence of large plant-trait data sets and remain largely untested. Here we formulate hypotheses on the controls of root: shoot biomass ratios (R:S), based on eco-evolutionary optimality principles, and assess them quantitatively by analysing data on nearly 30,000 observations of R:S. We analysed global R:S patterns using multiple linear regression models for woody and herbaceous species separately, considering as candidate predictors growing-season mean temperature (Tg), gross primary production (GPP), a measure of root-zone water capacity (RZWC), soil pH, sand content, aridity index (AI), and plant traits: vegetation height (H), leaf thickness (LT), leaf dry matter content (LDMC), specific leaf area (SLA), specific root length (SRL), and rooting depth (RRD). R:S was systematically greater in herbaceous plants. R:S decreased with Tg, GPP, and height but increased with sand content, RRD, and LDMC in both woody and herbaceous plants. However, AI and leaf thickness had opposing effects on R:S. RZWC and SLA were important in woody plants, while pH and SRL played a larger role in herbaceous plants. The models explained 13% (woody) and 31% (herbaceous) of R:S variation. The lower explanatory power for woody plants is likely influenced by unmeasured variations in (for example) forest age and canopy position. These empirical findings provide a step towards a quantitative theory of plant C allocation responses to resource availability and an improved C allocation scheme for ecosystem models.
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Journal articleLee Y, Yun HS, Ehsan M, et al., 2025,
Pendant-bearing detergents: strategies and membrane protein stabilization
, Trends in Chemistry, Vol: 7, Pages: 617-631, ISSN: 2589-5974Membrane proteins (MPs) are vital to many biological processes, making their atomic-level structures essential for drug discovery. Detergent micelles are commonly used in MP research, from extraction, purification, and structure determination. Recently, detergents featuring small pendant groups positioned at the hydrophilic–hydrophobic interface of the micelle have emerged as promising membrane mimetics. This review highlights recent developments in pendant-bearing detergents and explores the roles of pendant groups in MP stabilization. Hydrophobic or hydrophilic pendants enhance alkyl chain packing within micelle interiors through distinct mechanisms. Additionally, reactive pendants enable in situ structural modification of detergents. Pendant-bearing detergents represent valuable tools for MP structural studies and their rational design would pave the way for next-generation detergents to advance MP research.
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Journal articleLewisBrown E, Beatty H, Davis K, et al., 2025,
Improvements for better scaling of locally managed marine areas
, Conservation Biology, Vol: 39, ISSN: 0888-8892To protect and restore ecosystems at the speed and scale required to meet current environmental challenges, a greater understanding of how conservation initiatives spread from existing to new adopters is required. According to the diffusion of innovation theory, positive adopter-to-peer communication is a powerful driver of innovation spread, whereas negative communications hinder innovation spread. Aware of this, businesses regularly survey customers and respond accordingly to maximize company growth. Therefore, we used 2 consumer satisfaction research measures commonly used by businesses, importance–performance analysis (IPA), which measures performance on metrics that are most important to customers, and net promoter score (NPS), which measures likely spread through positive referrals, to study satisfaction among adopters of locally managed marine areas (LMMAs) in northeastern Madagascar. Our results identified 4 attributes of LMMAs that adopters viewed as important but rated as worsening over time (funding and livestock provided by a nongovernmental organization, conflict in the village, and connections with others). Adopters considered control over resources and fisheries restrictions important and high performing. Villagers rated their quality of life since adopting LMMAs positively on average, but NPS returned a negative result overall and a strongly negative score for nonleaders. Our findings can be used to improve the design and management of LMMAs, inform pre- and postproject impact assessments to minimize negative impacts from conservation initiatives, and increase the spread of conservation initiatives. More broadly, this study presents a novel outlook for increasing the adoption of conservation initiatives by framing adopters of conservation initiatives as akin to customers whose perceptions of conservation initiatives matter inherently and because of their power to influence the spread of conservation initiatives.
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Journal articleDorigatti I, Gaythorpe KAM, Cox VM, et al., 2025,
Priorities for modelling arbovirus transmission under climate change
, Trends in Molecular Medicine, Vol: 31, Pages: 885-894, ISSN: 1471-4914The transmission potential of arboviruses is extremely sensitive to environmental conditions. This sensitivity is due to both their intimate relationship with ectothermic vectors and, in many cases, also to the involvement of multiple host species in zoonotic transmission cycles. Here, we review how climate change will alter the transmission ecology and risk of these important infections. The challenge of predicting how climate change will impact these systems is daunting, but the need for tools to manage arbovirus risk under climate change is urgent and imperative. We argue that the development of climate-driven mechanistic models of disease transmission informed by empirical surveillance data is urgently needed to inform future responses and for generating the evidence that policy needs to tackle this global public health risk.
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Journal articleHui TJ, 2025,
Maximising the potential of temporal Ne estimation in long‐term population monitoring programmes
, Molecular Ecology Resources, Vol: 25, ISSN: 1755-098X -
Journal articleJordan S, Frankel G, Mishra V, 2025,
Citrobacter rodentium.
, Trends Microbiol, Vol: 33, Pages: 1132-1133 -
Journal articleJordan S, Frankel G, Mishra V, 2025,
Citrobacter rodentium
, TRENDS IN MICROBIOLOGY, Vol: 33, Pages: 1132-1133, ISSN: 0966-842X- Cite
- Citations: 1
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Journal articleKose Cetinkaya A, Sari FN, Buyuktiryaki M, et al., 2025,
Postnatal weight gain of premature small for gestational age versus appropriate for gestational age infants during NICU stay
, JOURNAL OF TROPICAL PEDIATRICS, Vol: 71, ISSN: 0142-6338 -
Journal articleToghani A, Frijters R, Bozkurt TO, et al., 2025,
Can AI modeling of protein structures distinguish between sensor and helper NLR immune receptors?
, NEW PHYTOLOGIST, Vol: 248, Pages: 17-23, ISSN: 0028-646X -
Journal articleKariuki R, Mirihana KA, Penman R, et al., 2025,
Interactions of nanoparticles with living and synthetic bio-membranes
, Chemical Society Reviews, ISSN: 0306-0012Interactions between nanomaterials and biointerfaces are of great interest across many research fields, including chemistry, physics, engineering, and biology, with applications from diagnostics to therapeutics, and in drug delivery systems. By tailoring nanomaterial properties via functionalisation, their efficacy can be enhanced for a variety of biomedical scenarios. Nanomaterial-based therapeutics, diagnostics, and theranostics display a common need to interact with biological tissue, i.e., they must make contact with, and often transverse, the external membrane of a cell or organism to elicit the desired response. As such, understanding nanoparticle (NP)–bio-membrane interactions is paramount to designing and optimising nanoparticle-based therapies and technologies for biological applications. Historically, in vivo investigations have proven to be challenging due to the complexity and intricate interactions involved with complete cell membranes. This has led researchers to employ model bio-membranes, which can be investigated using a range of in vitro experimental and theoretical techniques, to isolate the underpinning interaction mechanisms of NPs at the bio-interface. This review aims to unify the current literature regarding the biophysical interactions between inorganic and organic NPs and bio-membrane interfaces, including living and synthetic systems. The article will explore the role of membrane composition, NP morphology and chemistry, and the forces involved in interactions between the two entities. Identifying the fundamental influences of NP–membrane interactions, primarily synthetic NPs as these are more clinically applied, will allow for the more effective design of novel biomedical agents for future therapies.
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Journal articleShirgill S, Nieves DJ, Pike JA, et al., 2025,
Nano-org, a functional resource for single-molecule localisation microscopy data
, Nature Communications, Vol: 16, ISSN: 2041-1723The nanoscale organisation of proteins plays a key role in diverse cellular processes, including signalling, adhesion, and structural integrity. Single-molecule localisation microscopy (SMLM) is a super-resolution imaging technique that captures the spatial distributions of proteins in cells with nanometre precision, enabling detailed studies of protein clustering and architecture. However, comparing such data across experiments remains challenging due to a lack of curated, functional resources. Here we present a publicly accessible, curated, and functional resource, termed “nano-org”, containing SMLM data representing the nanoscale distributions of proteins in cells. Nano-org is searchable by comparing the statistical similarity of the datasets it contains. This unique functionality allows the resource to be used to understand the relationships of nanoscale architectures between proteins, cell types or conditions, supporting the development of the field of spatial nano-omics.
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Journal articleHui L, Ippolito K, Charalambous M, 2025,
Agency development and valuing peer perspectives: lessons from an intervention to enhance STEM university students’ feedback literacy
, Teaching & Learning Inquiry: The ISSOTL Journal, Vol: 13, ISSN: 2167-4779In order for students to benefit from feedback, they must develop their feedback literacy. To investigate the extent to which informing students about feedback knowledge and scaffolding practice for making sense of feedback increases feedback literacy, we conducted a skills-based intervention study. The results showed that the intervention increased students’ feedback knowledge, that is, their understanding about the purpose of feedback and the need to engage with it proactively. However, the intervention did not increase participants’ feedback literacy to a statistically significant extent. This may be due to the centrality of learner agency in feedback literacy and lack of time for this complex construct to develop. Findings from post-intervention focus group interviews revealed variation in students’ understanding and agency in relation to engaging with feedback and the importance of including various opportunities to develop agency as part of feedback literacy training, including through peer perspective sharing. Cultural influences on feedback processes appeared to be less significant than anticipated. Instead, individual differences, such as personal interpretations of feedback and associated emotional responses, were more likely to create barriers, and should therefore be considered when developing feedback literacy. This paper offers suggestions for implementing more effective feedback literacy development opportunities, including those that emphasise building on a foundation of feedback knowledge and the role of peers and peer feedback. We propose that future studies should develop an integrative approach to feedback literacy training that acknowledges the complexity and time demands of agency development.
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Journal articleWaititu JK, Nilsson K, Larrouy-Maumus G, et al., 2025,
RfaH is essential for virulence and adaptive responses in Yersinia pseudotuberculosis infection
, mBio, ISSN: 2161-2129We previously suggested that increased expression of the gene encoding transcriptional antiterminator RfaH during Yersinia pseudotuberculosis transcriptional reprogramming is necessary for adapting to persistent infection. In this study, we examined the role of RfaH in virulence and bacterial physiology under infection-relevant stress conditions, and identified genes differentially regulated in the absence of RfaH in Y. pseudotuberculosis. We employed a mouse infection model and phenotypic assays to test RfaH’s role in virulence and physiology, as well as RNA sequencing, including O-antigen biosynthesis-deficient strains. Our findings demonstrate that loss of RfaH significantly attenuates virulence, reducing the capacity of Y. pseudotuberculosis to establish persistent infection. RfaH expression is increased during the stationary growth phase and under various stress conditions, such as high osmolarity and bile salts, which are known to induce envelope stress. Functional assays revealed that the ΔrfaH strain displayed defects in motility and increased clumping, indicating altered surface properties affecting motility. Moreover, transcriptomic profiling of the ΔrfaH strain revealed a specific RfaH-dependent gene set after filtering out genes affected by O-antigen-related mutations, thereby minimizing confounding effects from surface structure alterations. These results suggest that RfaH influences a broader set of virulence and adaptation pathways beyond O-antigen regulation. Collectively, our findings suggest that RfaH is essential for the virulence and adaptive capacity of Y. pseudotuberculosis to colonize the host. This study provides insights into regulatory mechanisms that facilitate bacterial survival in hostile environments and highlights the importance of RfaH and its regulatory targets in the pathogenesis of Y. pseudotuberculosis.
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Journal articleCeballos-Escalera A, Llewellyn T, Richards J, et al., 2025,
A reference DNA barcode library for UK fungi associated with bark and ambrosia beetles
, Scientific Data, Vol: 12, ISSN: 2052-4463Bark and ambrosia beetles are ecologically important and widespread forest organisms. While flying between host plants and tunnelling into bark, they vector a high diversity of plant and insect-associated fungi within and between forests. These fungal communities live under the bark and rarely produce visible spore-bearing structures, making them difficult to sample and identify at scale. By combining passive insect trapping across the United Kingdom with individual beetle metabarcoding, we generated a reference DNA barcode library for fungi associated with over 1000 beetles, representing 25 native weevil species in the subfamily Scolytinae (Curculionidae). Sampling sites span longitudinal and latitudinal gradients, multiple forest types, and both natural and plantation forests. We use state-of-the-art fungal ITS2 OTU clustering and identification, resulting in 5274 identified fungal OTUs. This fungal diversity data can be used alongside extensive site and sample metadata to explore geographic and ecological biodiversity patterns. As these associations can be highly invasive and damaging, this resource provides a baseline to understand current fungal communities and monitor future changes.
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Journal articleBennison DJ, Chaudhary I, Chaudhuri D, et al., 2025,
GBP1 recruitment to actin-rich pedestals induced by extracellular Gram negative bacteria promotes pyroptosis.
, bioRxivThe IFNγ-induced GTPase guanylate binding protein 1 (GBP1) binds to lipopolysaccharide (LPS) on cytosolic Gram-negative bacteria and promotes pyroptosis via the recruitment and activation of caspase-4 on the bacterial outer membrane. Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC, respectively) are extracellular pathogens that also induce LPS- and caspase-4-dependent pyroptosis. However, whether GBP1 is involved in this process remains unknown. EPEC and EHEC adhere intimately to intestinal epithelial cells via avid interactions between the bacterial adhesin Intimin and Tir (Translocated intimin receptor), a type 3 secretion system effector protein. Intimin-mediated clustering of Tir triggers actin polymerisation, leading to pedestal-like structures at bacterial attachment sites. Here we show that GBP1 is recruited to actin pedestals in human cells infected with EPEC and EHEC in vitro and mouse colonocytes infected with the EPEC-like murine pathogen Citrobacter rodentium in vivo. GBP1-dependent caspase-4 trafficking to these sites leads to pyroptosis and IL-18 release. To dissect the mechanism of GBP1 trafficking, we engineered a chimeric receptor (FcγR-Tir) by combining the intracellular signalling domain of Tir and the extracellular ligand-binding domain of the Fcγ receptor. Clustering of FcγR-Tir with IgG-coated beads produced 'sterile' actin-rich pedestals that were sufficient to recruit GBP1 independently of bacteria. Our findings reveal that cytosolic GBP1 is mobilised to sites of pathogen-induced actin remodelling independently of LPS. We establish that GBP1 not only operates as a pattern-recognition receptor but also orchestrates effector-triggered immunity against pathogens that hijack the actin cytoskeleton.
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Journal articleSun Y, Burke TA, Dugdale HL, et al., 2025,
Long-term fitness effects of the early-life environment in a wild bird population
, BEHAVIORAL ECOLOGY, Vol: 36, ISSN: 1045-2249 -
Journal articleOno M, 2025,
TockyLocus: quantitative analysis of flow cytometric fluorescent timer data in Nr4a3-Tocky and Foxp3-Tocky mice
, Biology Methods & Protocols, Vol: 10, ISSN: 2396-8923Fluorescent Timer proteins undergo a time-dependent shift from blue to red fluorescence after translation, providing a temporal record of transcriptional activity in Timer reporter systems. While Timer proteins are well suited for studying dynamic cellular processes such as T cell activation using the Timer of-Cell-Kinetics-and-Activity (Tocky) framework, quantitative analysis of Timer-based flow cytometry data has yet to be fully standardised.In this study, we optimise quantitative analysis methods for the key parameter within the Tocky framework, Timer Angle, and introduce TockyLocus, an open-source R package that implements a five category scheme based on biologically grounded angular intervals (designated as Tocky Loci). This approach is validated using both simulated and experimental datasets and enables downstream statistical testing and visualisation of transcriptional dynamics in flow cytometry data. Using computational modelling of Timer protein kinetics, we define transcriptional dynamics in relation to key anchoring points in Timer Angle values at 0◦, 45◦, and 90◦. Comprehensive simulations with synthetic spike-in datasets further demonstrate the robustness of the five-locus approach, which captures the three key points and the intermediate regions between these points. Building on the TockyPrep pre processing framework, we systematically evaluated categorisation schemes ranging from three to seven loci on real-world datasets from Nr4a3-Tocky and Foxp3-Tocky mice. The five-locus model emerged as optimal, showing significant advantages in balancing biological interpretability and statistical robustness. Optimised algorithms implemented in the TockyLocus package now standardise quantitative analysisof Timer Angle data, enabling reproducible interpretation without reliance on arbitrary gating or complex assumptions. In summary, the five-locus categorisation of Timer Angle data effectively links underlying biological dynamics to the percentage of cells in eac
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Journal articleBradley RW, Nunez-Bajo E, Guder F, et al., 2025,
Synthetic Whole-Cell Bioelectronic Chemical Sensing with <i>In Situ</i> Genetic Computing
, CHEM & BIO ENGINEERING, Vol: 2, Pages: 501-510, ISSN: 2836-967X -
Journal articlePates NJ, Boyce BB, Crawley MJ, et al., 2025,
Using landscape biodiversity metrics to assess rewilding: A comparison of the Knepp Estate and an agricultural baseline at Boothby Wildland
, ECOLOGICAL SOLUTIONS AND EVIDENCE, Vol: 6 -
Journal articleMartin JS, Westneat DF, Nakagawa S, et al., 2025,
Measuring selection on reaction norms: Lack's principle and plasticity in clutch size
, EVOLUTION, ISSN: 0014-3820
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