Biology subjects

Wright, G.

Publications and source records attributed to Wright, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Exploring the antibiotic-producing capabilities of Canadian High Arctic bacteria

Microbial communities in harsh environments such as the Canadian high Arctic, remain a relatively unexplored source of antimicrobial natural products. In this study, we developed a pipeline for screening and evaluating bacterial isolates cultured from 23 Canadian high Arctic soil, sediment, and active-layer permafrost samples to discover antibacterial compounds. The pipeline incorporated an undergraduate studentsourcing program and produced created a collection of over 350 bacterial isolates with preliminary antibacterial activity. Following dereplication, whole genome sequencing and secondary screening by co-culture assays, five isolates were prioritized to test crude extracts for antibacterial activity. Among bioactive crude extracts from these isolates, the Pseudomonas isolate with the most potent activity against S. aureus was analyzed. Using liquid chromatography bioactivity guided fractionation, we identified a potential bioactive compound known as koreenceine A, a compound previously only isolated from a Pseudomonas from temperate soil and involved in gene expression of other their microbial community. Here we expanded the known antibiotic activity of koreenceine A and confirmed that a {triangleup}kecBCD genetic knockout of the putative biosynthetic gene cluster significantly abrogated the antibacterial activity.

microbiology↗

bioRxiv2026

Streptomyces induces unisexual reproduction of a major human fungal pathogen

Cryptococcus, a human pathogenic yeast, can undergo unisexual reproduction in the absence of compatible mating partners, yet this developmental program remains poorly understood. Here, we report that tunicamycin, a natural product produced by Streptomyces species, induces a complete unisexual reproductive cycle in different Cryptococcus species. Bacterial confrontation or purified tunicamycin trigger hyphal differentiation, meiotic recombination, and basidiospore formation, as confirmed by whole-genome sequencing and SNP analyses. We further demonstrate that tunicamycin-induced unisexual development requires canonical sexual regulators and meiotic machinery. Transcriptomic profiling reveals staged developmental reprogramming characterized by early induction of stress- and cell cycle-associated genes, followed by enrichment of genes in the filamentation-related pathways. This capacity varies among natural isolates of C. neoformans and was conserved in Cryptococcus gattii. Together, our findings demonstrate that a bacterial metabolite can activate meiotically competent unisexual reproduction, highlighting interkingdom chemical signaling as a potential driver of fungal evolution in natural environments.

microbiology↗

bioRxiv2026

Whole slide image analysis of the endometrial decidual reaction reveals multiscale perturbations associated with miscarriage

The inflammatory decidual reaction renders the cycling endometrium transiently permissive for embryo implantation before transforming it into the decidua, the maternal bed accommodating the fetal placenta during pregnancy. Disruptions in decidual tissue remodeling are linked to miscarriage and other pregnancy disorders. However, endometrial assessment is hampered by a lack of affordable technologies capable of mapping the spatiotemporal dysregulation of this dynamic and complex tissue. Employing a graph neural network on whole slide images of 493 CD56-immunostained endometrial samples, Endometronome was developed as a deep learning tool to spatially track the decidual reaction and provide accurate estimates of marker gene expression. When applied to 2,690 additional biopsies, this model consistently identified morphological correlates of prior miscarriage burden, a proxy for future risk. Further, a morphological signature indicative of metabolic glandular impairment discriminated between clinical miscarriage presentations. These findings illustrate how advanced imaging analysis of routine histology can transform miscarriage prevention strategies.

pathology↗

bioRxiv2026

DCAFA: Differential Community Abundance and Feature Analysis for Histological Images

Histological images are composed of diverse local structures such as cells, glands, or tissue patches, whose organisation and relative abundance reflect underlying biological processes. While most computational approaches focus on analysing individual features, many clinically relevant signals arise from changes in the composition of these structures rather than isolated measurements. This motivates the need for explicitly modelling how groups of similar instances vary across samples and relate to outcomes. We present DCAFA (Differential Community Abundance and Feature Attribution Analysis), a regression-based framework for analysing hierarchical biomedical data through both compositional and feature-level perspectives. DCAFA groups instances into latent communities representing recurring morphological or phenotypic patterns, and then performs two complementary analyses: (i) community composition analysis, which identifies groups that are enriched or depleted across outcomes, and (ii) feature attribution analysis, which quantifies how instance-level features relate to outcomes directly or within specific communities. Both use generalised linear and mixed-effects models, enabling covariate adjustment and inference through effect sizes, confidence intervals, and false discovery rate control. We demonstrate the utility of DCAFA across multiple biomedical settings, including endometrial histopathology, spatial transcriptomics, multiplex immunofluorescence imaging, and predefined cell-type analyses in colorectal cancer. These examples identify interpretable compositional shifts and context-specific feature associations that are not captured by conventional feature-based approaches. By unifying differential abundance testing and feature attribution within a single statistical framework, DCAFA serves as an openly available toolbox that provides a practical and interpretable means of linking tissue composition with clinical or molecular outcomes in biomedical imaging data. Code available at: https://github.com/wgrgwrght/DCAFA

bioinformatics↗

bioRxiv2026

A computational model for quantifying instability of tandem repeats across the genome

Tandem repeats (TRs) exhibit high levels of somatic mosaicism, which is increasingly recognized as an important modifier of repeat expansion disorders. Long-read sequencing can capture full-length repeat alleles, yet robust frameworks for quantifying instability across TRs genome-wide are still needed. Here, we introduce a general-purpose model for quantifying TR instability in a given long-read sequencing dataset, without explicitly distinguishing biological mosaicism from technical noise, and which is broadly applicable to both simple and structurally complex loci. This model accurately characterizes allelic instability at each TR locus by representing the distribution of read-to-consensus deviations for each allele. Using HiFi sequencing data from 256 HPRC cell line samples, we fitted models for 617,007 TR loci, including known pathogenic repeats. We observe that instability levels are generally low, but vary substantially across individual TRs, and are driven more strongly by repeat composition than overall repeat length. Furthermore, we applied our method to targeted PureTarget long-read data from samples with known repeat expansions and identified significant mosaicism in the majority of expanded alleles. Our model offers a practical way to quantify instability of tandem repeats across the genome and to detect unusually unstable repeat alleles.

bioinformatics↗

bioRxiv2026

CD31+ T-cells express greater VEGF-A and CXCR4 levels than CD31- counterparts with VEGF-A expression exacerbated with advancing age

CD31+ T-cells reportedly possess angiogenic properties. These cells have recently been termed angiogenic T-cells (TANG). Advancing age is associated with altered circulating T-cell phenotypes, including TANG, and reduced angiogenesis. We examined various TANG subsets (CD3+, CD4+, CD8+), and their VEGF-A intracellular content in young (n=16, 18-30 years) and older (n=16, 50-65 years) male adults using flow cytometry. Cardiorespiratory fitness ([V]O2max) was quantified in all participants using a graded cycling ergometry test to volitional exhaustion. Resting blood samples were collected to measure circulating IL-6 and cytomegalovirus serostatus. CD31+ T-cells (TANG) contained more VEGF-A than CD31- T-cells (CD31+: 9374 {+/-} 8587 AU vs CD31-: 8722 {+/-} 8149 AU, p = 0.021) which was also exhibited in CD4+ and CD8+ subsets. Older adults possessed fewer CD4+ TANG cells as a proportion of total CD4+ T-cells than younger adults (young: 35 {+/-} 11%; older: 24 {+/-} 9%, p = 0.004), and CD3+ and CD4+ TANG subsets from older adults exhibited higher VEGF-A levels than younger adults (CD3+CD31+: young: 6081 {+/-} 4001 AU; older: 13426 {+/-} 10945 AU, p = 0.019; CD4+CD31+: young: 6373 {+/-} 3972 AU; older: 15660 {+/-} 12829 AU, p = 0.011). TANG cells were not associated with circulating IL-6, and TANG VEGF-A content was not associated with[V] O2max. Advancing age is associated with a pathological TANG phenotype, which may contribute to age-related inflammation and warrants further investigation as a potential therapeutic target.

immunology↗

bioRxiv2026

GOTFlow: Learning Directed Population Transitions from Cross-Sectional Biomedical Data with Optimal Transport

MotivationMany biological and clinical processes are dynamic, yet most datasets are cross-sectional, capturing populations at discrete states rather than tracking individuals over time. This makes it difficult to quantify how populations change across developmental, physiological, or disease-associated conditions. Existing trajectory and transport-based methods often rely on fixed feature spaces, assumptions tailored to transcriptomic time-course data, or approximately linear progression, limiting their ability to model heterogeneous and unbalanced transitions across diverse biomedical modalities. Flexible methods are needed that can infer directed population-level change from cross-sectional data while retaining biological interpretability. ResultsWe present GOTFlow, a framework for learning directed population transitions from cross-sectional biomedical data using graph-constrained optimal transport in a learned latent space. GOTFlow integrates representation learning with unbalanced optimal transport to jointly estimate embeddings and transport couplings between biological states. This enables hypothesis-driven modelling of progression structures while accommodating non-linear geometry, branching relationships, and changes in population mass. From the inferred transport plans, GOTFlow derives interpretable summaries of dynamics, including drift vectors quantifying transitions, and feature-level transported changes that highlight molecular drivers of progression. In synthetic data, GOTFlow recovered known transitions with strong agreement between inferred and ground-truth drifts. Across three biological applications, endometrial remodelling, breast cancer risk progression, and prion disease, GOTFlow identified state-to-state transitions and biologically meaningful feature shifts reflecting impaired decidualisation, increasing cancer risk, and neurodegenerative progression. These results establish GOTFlow as a general and interpretable framework for analysing directed population dynamics from cross-sectional data. AvailabilityCode available at: https://github.com/wgrgwrght/GOTFlow

bioinformatics↗

bioRxiv2026

BEEhaviourLab: A high-throughput platform for sublethal stressor screening in insects

Behavioural responses often provide the earliest detectable signs of physiological stress yet quantifying them at scale remains challenging. Acoustic behaviours such as buzzing are central to insect locomotion and communication but are rarely measured systematically, and their potential as sensitive indicators of environmental stress remains largely unexplored. Here, we test whether changes in insect acoustic behaviour can reveal sublethal effects of pesticide exposure. Using a newly developed automated behavioural platform (BEEhaviourLab), we recorded synchronised video and audio from insects, enabling simultaneous, high-throughput quantification of locomotor activity and buzzing behaviour across multiple individuals and species without the need for tagging. We applied this system to characterise the effects of the veterinary antiparasitic moxidectin on the bumble bee Bombus terrestris. Acute contact exposure produced dose-dependent reductions in locomotion and buzzing behaviour at concentrations below lethal thresholds. Acoustic measures detected behavioural disruption with sensitivity comparable to video-based activity metrics, demonstrating that buzzing behaviour provides a sensitive and previously unused indicator of neurotoxic stress. More broadly, scalable multimodal behavioural phenotyping enables subtle behavioural disruption to be detected across large experiments, opening new opportunities to incorporate acoustic endpoints into studies of animal behaviour, environmental stress, and ecological risk assessment.

animal behavior and cognition↗

bioRxiv2025

Pollen sterols are highly diverse but phylogenetically conserved

Sterols regulate cell membrane fluidity and are precursors for hormone and secondary metabolite production in plants, but plant sterols also have a critical role as nutrients in herbivores. Here we describe the distribution of 78 different sterols from pollen of 295 UK wildflower taxa and use this data to develop an evolutionary rationale for the diversity of sterols in pollen compared to vegetative tissues. The sterolome was a function of plant lineage and conserved in groups as high as subfamily. Insect herbivores are auxotrophic for sterols, and notably bees can not modify them therefore rely on dietary sources, primarily pollen, to meet their metabolic needs. Most pollen in the present study contained high proportions of {Delta}5 sterols including {beta}-sitosterol, 24-methylenecholesterol and isofucosterol, which are important sterols for bees. The sterols recorded in honey bees occurred in the pollen of only 68% of plant taxa, however, none matched these proportions exactly suggesting they must forage pollen from multiple plant taxa to satisfy their sterol requirements. We conclude that there is evidence for pollen sterol composition being the result of diverse driving forces including plant lineage and pollinator nutritional requirements.

biochemistry↗

bioRxiv2024

Element partitioning, element localisation and transcriptome responses of date palms exposed to NaCl

Date palm (Phoenix dactylifera L.) is an economically important fruit crop in many (semi)arid regions. Large intra-species variation in susceptibility to NaCl has been reported. Controlled experiments were conducted to evaluate sodium (Na) and chlorine (Cl) partitioning in two-year old plants of six date palm varieties and to determine tissue location of Na and Cl and transcriptome responses to NaCl of two varieties. The largest Na concentrations were found in secondary roots, especially under NaCl treatment. By contrast, only small differences in within-plant partitioning of Cl were observed with less differences between varieties than for Na. Variety Sultana had the largest Na translocation factor. The variety Khalas exhibited better restriction of Na mobility, which may be a consequence of Na hotspots in roots, presumably immobilising Na in roots, which were absent in Sultana. In the root, shoot base and lower part of leaves, Cl accumulated in fibre bands and sclerenchyma sheaths of vascular bundles. RNAseq analysis revealed that Sultana and Khalas respond very differently to NaCl: Khalas modified expression of NaCl-specific genes in both roots and leaves, while Sultana responded manly in leaves. Gene ontology analysis showed that the expression changes for genes linked with photosynthesis and carbohydrate metabolism predominated as a response to NaCl. In Khalas, differentially expressed genes encoding for metal transporters and those reported to be involved in heat, salt and osmotic stress response were found. Large variability in Na and Cl accumulation in different date palm varieties may have practical agronomical consequences.

plant biology↗

bioRxiv2024

Shifts in Naturalistic Behaviors Induced by Early Social Isolation Stress are Associated with Adult Binge-like Eating in Female Rats

Binge eating (BE) is a highly pervasive maladaptive coping strategy in response to severe early life stress such as emotional and social neglect. BE is described as repeated episodes of uncontrolled eating and is tightly linked with comorbid mental health concerns. Despite social stressors occurring at a young age, the onset of BE typically does not occur until adulthood providing an interval for potential therapeutic intervention. Currently, our knowledge of longitudinal noninvasive digital biomarkers predictive of BE needs further development. Monitoring longitudinal impacts of adolescent social isolation stress on naturalistic behaviors in rats will enable the identification of noninvasive digital markers of disease progression to predict adult eating strategies. Recognizing adolescent naturalistic behaviors shaped by social stress informs our understanding of the underlying neurocircuits most effected. This study aimed to monitor and identify longitudinal behavioral shifts to enhance predictive capabilities in a rat model of social isolation stress-induced BE. We placed Paired (n=12) and Socially Isolated (SI, n=12) female rats in observational home cages weekly for seven weeks to evaluate the effect of SI on 10 naturalistic behaviors. All 10 naturalistic behaviors were simultaneously detected and tracked using Noldus Ethovision XT automated recognition software. Composite phenotypic z-scores were calculated by standardizing all 10 behaviors. When transitioning into adulthood, all rats underwent conventional emotionality testing and were exposed to a Western-like high fat diet (WD, 43% kcal from fat) to evaluate BE. Longitudinal assessments revealed SI-induced shifts in adolescent phenotypic z-scores and that sniffing, unsupported rearing, jumping, and twitching were the most susceptible to SI. SI increased emotionality compared to the Paired controls. Finally, we identified adolescent twitching as a digital biomarker of adult WD consumption. This study employed novel approaches to identify early life predictive biomarkers of adult eating strategies and laid a foundation for future investigations.

neuroscience↗

bioRxiv2024

Darwin's Naturalization Conundrum explained by gradients of environmental stress and disturbance

Darwins Naturalization Conundrum (DNC) states that non-native species closely related to the native community are either more likely to succeed because shared adaptations help them overcome environmental filtering, or less likely to succeed because of strong competition with their native relatives. Despite extensive research, no general patterns have so far emerged. One reason may be that the relative importance of competition and environmental filtering depends on environmental conditions. To test this hypothesis, we conducted a global assessment of DNC examining patterns of phylogenetic relatedness of non-native plant species to the native community along gradients of elevation and anthropogenic disturbance in mountains. Phylogenetic distance of non-native to native species decreased with increasing elevation and in disturbed plant communities. Our results help resolve DNC by showing that the environmental context sets expectations for patterns of relatedness between non-native and native species and helps illuminate the ecological and evolutionary processes generating these patterns.

ecology↗

bioRxiv2024

A comparison of super-resolution microscopy techniques for imaging tightly packed microcolonies of an obligate intracellular bacterium

Conventional optical microscopy imaging of obligate intracellular bacteria is hampered by the small size of bacterial cells, tight clustering exhibited by some bacterial species and challenges relating to labelling such as background from host cells, a lack of validated reagents, and a lack of tools for genetic manipulation. In this study we imaged intracellular bacteria from the species Orientia tsutsugamushi (Ot) using five different fluorescence microscopy techniques: standard confocal, Airyscan confocal, instant Structured Illumination Microscopy (iSIM), three-dimensional Structured Illumination Microscopy (3D-SIM) and Stimulated Emission Depletion Microscopy (STED). We compared the ability of each to resolve bacterial cells in intracellular clumps in the lateral (xy) axis, using full width half maximum (FWHM) measurements of a labelled outer membrane protein (ScaA) and the ability to detect small, outer membrane vesicles external to the cells. We next compared the ability of each technique to sufficiently resolve bacteria in the axial (z) direction and found 3D-STED to be the most successful method for this. We then combined this approach with a custom 3D cell segmentation and analysis pipeline using the open-source, deep learning software, Cellpose to segment the cells and subsequently the commercial software Imaris to analyze their 3D shape and size. Using this combination, we demonstrated differences in bacterial shape, but not their size, when grown in different mammalian cell lines. Overall, we compare the advantages and disadvantages of different super-resolution microscopy techniques for imaging this cytoplasmic obligate intracellular bacterium based on the specific research question being addressed.

microbiology↗

bioRxiv2024

The Caenorhabditis elegans bacterial microbiome influences microsporidia infection through nutrient limitation and inhibiting parasite invasion

Microsporidia are eukaryotic obligate intracellular parasites that infect most animals including humans. To understand how the microbiome can impact microsporidia infection, we tested how bacterial isolates that naturally occur with Caenorhabditis elegans influence infection by the microsporidian Nematocida parisii. Nematodes exposed to two of these bacteria, Chryseobacterium scopthalmum and Sphingobacterium multivorum, exhibit reduced pathogen loads. Using untargeted metabolomics, we show that unsaturated fatty acid levels are disrupted by growth on these bacteria and that supplementation with the polyunsaturated fatty acid linoleic acid can restore full parasite growth in animals cultured on S. multivorum. We also found that two isolates, Pseudomonas lurida and Pseudomonas mendocina, secrete molecules that inactivate N. parisii spores. We determined that P. lurida inhibits N. parisii through the production of massetolides. We then measured 53 additional Pseudomonas strains, 64% of which significantly reduced N. parisii infection. A mixture of Pseudomonas species can greatly limit the amount of infection in C. elegans populations over many generations. Our findings suggest that interactions between bacteria and N. parisii are common and that these bacteria both modulate host metabolism and produce compounds that inhibit microsporidia infection.

microbiology↗

bioRxiv2022

A single extracellular loop of FoxA controls ligand specificity, uptake, and signaling in Pseudomonas aeruginosa

The outer membrane of Gram-negative bacteria prevents many antibiotics from reaching intracellular targets. However, some antimicrobials can take advantage of iron import transporters to cross this barrier. We showed previously that the thiopeptide antibiotic, thiocillin, exploits the nocardamine (ferrioxamine E) xenosiderophore transporter, FoxA, of the opportunistic pathogen Pseudomonas aeruginosa for uptake. Here we show that FoxA also transports the xenosiderophore bisucaberin and describe at 2.5 [A] resolution the first crystal structure of bisucaberin bound to FoxA. Bisucaberin is distinct from other siderophores because it forms a 3:2 rather than 1:1 siderophore-iron complex. Mutations in a single extracellular loop of FoxA differentially affected nocardamine, thiocillin, and bisucaberin binding, uptake, and signal transduction. These results show that in addition to modulating ligand binding, the extracellular loops of siderophore transporters are of fundamental importance for controlling ligand uptake and its regulatory consequences, which has implications for the development of siderophore-antibiotic conjugates to treat difficult infections.

microbiology↗

bioRxiv2022

Temporal responses of bumblebee gustatory neurons encode sugar identity

The sense of taste permits the recognition of valuable nutrients and the avoidance of potential toxins. Models of gustatory coding propose that within modalities (e.g. sweet, bitter, etc.), taste ligands are not distinct stimuli. However, these models are based on data from mice or flies that have omnivorous, non-specialist diets. A specialist feeder might, however, be expected to have acuity within modality if stimulus resolution was critical to survival. Previously, we found that bumblebees have a specialized mechanism for sensing sugars whereby two gustatory receptor neurons (GRNs) within the galeal sensilla of the bees mouthparts exhibit burst of spikes. Here, we show that the temporal firing patterns of these GRNs separate sugars into four distinct groups that correlate with sugar nutritional value and palatability. We also identified a third GRN that responded to stimulation with relatively high concentrations of fructose, sucrose, and maltose. Sugars that were non-metabolizable or toxic suppressed the responses of bursting GRNs to sucrose. These abilities to encode information about sugar value are a refinement to the bumblebees sense of sweet taste that could be an adaptation that enables precise calculations of the nature and nutritional value of floral nectar.

neuroscience↗

bioRxiv2021

Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family

The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an AAC(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment.

microbiology↗

bioRxiv2021

Accurate analysis of short read sequencing in complex genomes: A case study using QTL-seq to target blanchability in peanut (Arachis hypogaea)

Next Generation sequencing was a step change for molecular genetics and genomics. Illumina sequencing in particular still provides substantial value to animal and plant genomics. A simple yet powerful technique, referred to as QTL sequencing (QTL-seq) is susceptible to high levels of noise due to ambiguity of alignment of short reads in complex regions of the genome. This noise is particularly high when working with polyploid and/or outcrossing crop species, which impairs the efficacy of QTL-seq in identifying functional variation. By filtering loci based on the optimal alignment of short reads, we have developed a pipeline, named Khufu, that substantially improves the accuracy of QTL-seq analysis in complex genomes, allowing de novo variant discovery directly from bulk sequence. We first demonstrate the pipeline by identifying and validating loci contributing to blanching percentage in peanut using lines from multiple related populations. Using other published datasets in peanut, Brassica rapa, Hordeum volgare, Lactua satvia, and Felis catus, we demonstrate that Khufu produces more accurate results straight from bulk sequence. Khufu works across species, genome ploidy level, and data types. In cases where identified QTL were fine mapped, the fine mapped region corresponds to the top of the peak identified by Khufu. The accuracy of Khufu allows the analysis of population sequencing at very low coverage (<3x), greatly decreasing the amount of sequence needed to genotype even the most complex genomes.

genomics↗