Biology subjects

Wright, K.

Publications and source records attributed to Wright, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Isolation and characterisation of Lytic Jumbo Klebsiella phage BMPCR_005026

Background: Klebsiella pneumoniae is a key causative agent of multidrug resistant nosocomial infections. Bacteriophages offer a promising alternative treatment, but the diversity of Klebsiella species requires the characterisation of a broad range of phages, particularly the poorly characterised jumbo phages. Materials and Methods: Phage BMCPR_005026 was isolated from sewage against Klebsiella pneumoniae. Whole genome sequencing, transmission electron microscopy and host range analysis against a diverse set of 40 clinically relevant Klebsiella strains were used to characterise the phage. Results: The virion had a myovirus morphology and genomic analysis placed it within an undefined family in Caudoviricetes where it forms a new species within the genus Alcyoneusvirus. BMCPR_005026 could form plaques on 3 of the 40 Klebsiella strains tested (7.5%) and formed halos. Conclusion: BMCPR_005026 represents a new species of phage within the genus Alcyoneusvirus with activity against 3 Klebsiella KL-types.

microbiology↗

bioRxiv2026

Genetic depletion in zebrafish uncovers requirement for septins in haematopoiesis

Haematopoiesis and differentiation of immune cells from haematopoietic stem and progenitor cells (HSPCs) are essential to core aspects of health and disease. A key player in haematopoiesis and HSPC differentiation is the cytoskeleton, which governs cell division and lineage bias. Despite insights using mouse models, regulation of haematopoiesis by the septin cytoskeleton is mostly unknown. Septins are unconventional filament forming proteins best known for roles in cell division and host defence. To investigate septin-mediated host defence in vivo, we generated septin-deficient zebrafish models for infection with Mycobacterium marinum. Unexpectedly, septin-deficient larvae were protected from mycobacterial infection due to significantly increased macrophage numbers, reduced cell death, and enhanced inflammatory responses. Underlying this, we found that septin-deficient larvae produce significantly more HSPCs and show myeloid lineage bias, establishing a requirement for septins in haematopoiesis. In agreement with classical HSPC hierarchy, increased myeloid production in septin-deficient larvae is at the expense of erythroid lineage production. Our findings that septins play a role in haematopoiesis is consistent with hallmarks of haematological disorders in which septin dysfunction has been implicated, including acute myeloid leukaemia, myelodysplastic syndrome, and platelet disorder Bernard-Soulier syndrome. These results highlight zebrafish as a new model to investigate septin-mediated haematopoiesis and application of septin-based medicines to treat blood disorders.

cell biology↗

bioRxiv2026

Microbiome stability in wild and rehabilitated insectivorous bats revealed by shotgun metagenomics

BackgroundWildlife rehabilitation can influence host-associated microbiota, yet little is known about how the gut microbiome of insectivorous bats responds to rehabilitation during temporary managed care. This study applied shotgun metagenomics to evaluate the impact of temporary managed care on the gut microbiome of wild and rehabilitated bats in Yorkshire, UK. ResultsWe analysed 25 faecal metagenomes from Myotis daubentonii, Pipistrellus pipistrellus, Nyctalus noctula and N. leisleri, including wild baseline bats and bats sampled during temporary managed care (1-49 days in rehabilitation). Microbial communities clustered strongly by host species and roost location, but not by rehabilitation status. Bacterial alpha diversity did not differ between wild bats, and bats in care (H = 2.30, p = 0.32). Archaeal communities were highly uniform across samples, showing far lower interindividual variation than bacterial communities (12.2% vs. 41.8% coefficient of variation). Rehabilitated bats showed increased relative abundance of Yersiniaceae and Lactobacillaceae, while environmental families such as Pseudomonadaceae and Erwiniaceae decreased, indicating modest but non-disruptive changes consistent with a controlled diet and reduced environmental exposure. ConclusionsAcross temporary managed care, the core gut microbiome of insectivorous bats remained stable, demonstrating notable microbial resilience. These findings provide an important baseline for monitoring microbiome health in wildlife rehabilitation and supporting post-release conservation programmes in the UK and beyond.

microbiology↗

bioRxiv2026

mRNAfold: Co-optimization of Global Stability, Local Structure, and Codon Choice via Suboptimal Folding

mRNA medicines hold great promise, but designing sequences with high translation efficiency, robust in-solution stability, and manufacturability remains a major challenge due to the vast combinatorial space of synonymous coding sequences. Computational approaches such as mRNA folding algorithms have emerged as powerful tools by co-optimizing for in-solution stability and translation efficiency, yet current methods face important limitations. Here, we present "mRNAfold", an improved mRNA folding algorithm and software package that addresses these gaps by enabling efficient exploration of diverse near-optimal solutions, incorporating untranslated regions (UTRs), parallel execution, and supporting tunable control over local structural features across the mRNA. Thermodynamically optimized mRNAs from mRNAfold were more stable ({approx} 2-fold) in-solution than those generated by simple GC maximization for the same encoded protein. In addition, mRNAs designed to vary local structure near the start codon while maintaining consistent structure and codon optimality elsewhere showed a complex relationship between local structure near the start codon and protein production in cells. We observed no impact of structure in the start codon region for a set of mRNAs with high codon optimality, but it did impact protein production for a set of mRNAs with lower codon optimality. Together, these results underscore the potential of structure-aware, multi-objective design to improve mRNA medicines and offer a framework for exploring how sequence, structure, and expression are interrelated.

bioinformatics↗

bioRxiv2025

Rolling out plaque-2-sequence: a single plaque sequencing approach enabling rapid, low-cost sequencing of phages directly from plaques

Rapid, accurate, and scalable sequencing of bacteriophage genomes is critical to advance phage therapy, build phage biobanks and understand phage genomic diversity. Current methods are based on sequencing and assembling complete bacteriophage genomes using short- or long-read technologies. However, current protocols require large DNA input and are cost prohibitive which limits their application to phage collections that typically are large and have low-biomass. In order to address this we have developed plaque-2-sequence, a robust and cost-effective workflow for high-throughput phage genome sequencing that will transform the speed and cost of attaining phage genomes. Plaque-2-sequence combines low-input transposase-based library preparation, amplification, nanopore sequencing and optimised assembly steps tailored to phage genomes. We applied the method to phages isolated on seven genetically diverse bacterial hosts; Escherichia, Pseudomonas, Synechococcus, Enterococcus, Klebsiella , Serratia and Enterobacter. High quality genome assemblies were validated using CheckV and benchmarking against previously sequenced phage isolates. Compared to standard Illumina sequencing, plaque-2-sequence offers [~]10-fold savings in sequencing price for individual labs. Furthermore, it substantially decreases the time required to produce a phage genome, once a plaque is obtained. Offering the ability to routinely obtain hundreds of phage genome sequences a week, with minimal hands-on time. Plaque-2-sequence enables systematic genomic characterisation of phage isolates, facilitating taxonomic classification, for the development of large scale phage biobanks. Impact StatementHere we have optimised a method for high-throughput sequencing of bacteriophage genomes from single plaques (plaque-2-sequence). We present a robust, high-throughput and cost-effective workflow. Plaque-2-sequence combines low-input transposase-based library preparation, amplification, nanopore sequencing and optimised assembly steps tailored to phage genomes. We demonstrate the scalability of this approach by sequencing over 100 phages from multiple bacterial hosts. This marks a step-change for the field, allowing phage genome sequencing to keep pace with phage isolation rates, and transforming how rapidly we can explore and understand phage genomic diversity.

microbiology↗

bioRxiv2025

Proximity biotinylation at the host-Shigella interface reveals UFMylation as an antibacterial pathway.

Host cells contest invasion by intracellular bacterial pathogens with multiple strategies that recognise and / or damage the bacterial surface. To identify novel host defence factors targeted to intracellular bacteria, we developed a versatile proximity biotinylation approach coupled to quantitative mass spectrometry that maps the host-bacterial interface during infection. Using this method, we discovered that intracellular Shigella and Salmonella become targeted by UFM1-protein ligase 1 (UFL1), an E3 ligase that catalyses the covalent attachment of Ubiquitin-fold modifier 1 (UFM1) to target substrates in a process called UFMylation. We show that Shigella antagonises UFMylation in a dual manner: first, using its lipopolysaccharide (LPS) to shield from UFL1 recruitment; second, preventing UFM1 decoration by the bacterial effector IpaH9.8. Absence of UFMylation leads to an increase of bacterial burden in both human cells and zebrafish larvae, suggesting that UFMylation is a highly conserved antibacterial pathway. Contrary to canonical ubiquitylation, the protective role of UFMylation is independent of autophagy. Altogether, our proximity mapping of the host-bacterial interface identifies UFMylation as an ancient antibacterial pathway and holds great promise to reveal other cell-autonomous immunity mechanisms.

microbiology↗

bioRxiv2025

Telomerase reverse transcriptase is required for resistance to mycobacterial infection

Age is an important risk factor for infections such as tuberculosis (TB). Telomerase is expressed in immune cells yet leukocyte telomere length declines during ageing suggesting an age-dependent loss of telomerase activity in the immune system. Leukocyte telomere length has been correlated with worse outcomes in TB patients, however the mechanisms linking telomere biology to TB susceptibility and response to therapy are unexplored. Here we use the zebrafish-Mycobacterium marinum model to investigate the role of telomerase in TB resistance. We find depletion and inhibition of Tert, the catalytic subunit of telomerase, increases bacterial burden in zebrafish embryos. The Tert depletion infection susceptibility phenotype could not be rescued by p53 or STING depletion suggesting a non-canonical role for Tert in controlling mycobacterial infection. Consistent with a previously described role for Tert in developmental hematopoiesis, we find Tert is necessary for demand-driven emergency myelopoiesis to support containment of extended mycobacterial infection. Our findings establish a previously undescribed role for host telomerase in supporting infection demand-driven hematopoiesis to control infection.

immunology↗

bioRxiv2025

Prognostically favorable immune responses to ovarian cancer are distinguished by self-reactive intra-epithelial plasma cells

Tumor-infiltrating B cells (TIL-Bs) are strongly associated with patient survival; however, the underlying mechanisms are poorly understood. Using integrated single-cell and spatial biology approaches, we defined at clonal resolution the molecular phenotypes, tumor reactivity patterns, and microenvironmental locations of TIL-Bs in high-grade serous ovarian cancer (HGSC). Prognostic benefit was associated with a TIL-B-rich tumor microenvironment with marked infiltration of malignant epithelium by plasma cells (PCs). PCs spanned five molecular phenotypes; exhibited high rates of somatic hypermutation and clonal expansion; and expressed predominantly IgG1 antibodies recognizing broadly expressed nuclear, cytoplasmic, and cell surface self-antigens. Many PC-derived antibodies were polyreactive. Self- and poly-reactive TIL-Bs penetrated tumor epithelium and stroma and expressed interferon-stimulated genes, indicating strong in situ activation. The self- and poly-reactive nature of TIL-B responses, reminiscent of autoimmune disease, may provide a means for the immune system to combat tumor heterogeneity and could potentially be harnessed for more effective immunotherapy.

cancer biology↗

bioRxiv2024

A diverse landscape of FGFR alterations and co-mutations defines novel therapeutic strategies in pediatric low-grade gliomas

Alterations in Fibroblast growth factor receptor (FGFR)-family proteins frequently occur as oncogenes in many cancers, including a subset of pediatric gliomas. Here, we performed a genomic analysis of 11,635 gliomas across ages and found that 4.5% of all gliomas harbor FGFR alterations including structural variants (SV) and single nucleotide variants (SNV), with an incidence of almost 10% in pediatric gliomas. FGFR family members are differentially enriched by age, tumor grade, and histological subtype, with FGFR1-alterations associated with glioneuronal histologies and pediatric low-grade gliomas. Across development, we find FGFR1 expression in both neuronal and glial precursors, while FGFR3 expression is largely restricted to astrocytic lineages. Leveraging novel isogenic model systems, we confirm FGFR1 alterations to be sufficient to activate MAPK and mTOR signaling, drive gliomagenesis, activate neuronal transcriptional programs and exhibit sensitivity to MAPK pathway inhibitors, including pan-FGFR inhibitors. Models driven by FGFR1 SVs exhibited different patterns of sensitivity compared to those driven by SNVs. Finally, we performed a retrospective analysis of clinical responses in children diagnosed with FGFR-driven gliomas and found that targeted MAPK or FGFR-inhibition with currently available inhibitors is largely associated with stability of disease. This study provides key insights into the biology of FGFR1-altered gliomas, therapeutic strategies to target them and associated challenges that still need to be overcome.

cancer biology↗

bioRxiv2024

Longitudinal analysis of body weight reveals homeostatic and adaptive traits linked to lifespan in diversity outbred mice

Dense temporal measurements of physiological health using simple and consistent assays are essential to characterize biological processes associated with aging and evaluate the effectiveness of interventions on these processes. We measured body weight in 960 genetically diverse mice, every 7-10 days over the full course of their lifespan. We used a state space model to characterize the trajectories of body weight throughout life and derived 10 novel traits capturing the dynamics of body weight that are both associated with lifespan and heritable. Genetic mapping of these traits identified 12 genomic loci, none of which were previously mapped to body weight. We observed that the ability to stabilize body weight, despite fluctuations in energy intake and expenditure, is positively associated with lifespan and mapped to a genomic locus linked to energy homeostasis. Our results highlight the importance of dense longitudinal measurements of physiological traits for monitoring health and aging.

physiology↗

bioRxiv2022

A comprehensive proteomic and bioinformatics analysis of human spinal cord injury plasma identifies proteins associated with the complement cascade and liver function as potential prognostic indicators of neurological outcome

1.1.1. IntroductionSpinal Cord Injury (SCI) is a major cause of disability, with complications post-injury often leading to life-long health issues with need of extensive treatment. Neurological outcome post-SCI can be variable and difficult to predict, particularly in incomplete injured patients. The identification of specific SCI biomarkers in blood, may be able to improve prognostics in the field. This study has utilised proteomic and bioinformatics methodologies to investigate differentially expressed proteins in plasma samples across human SCI cohorts with the aim of identifying prognostic biomarkers and biological pathway alterations that relate to neurological outcome. 1.2. Methods and MaterialsBlood samples were taken, following informed consent, from ASIA impairment scale (AIS) grade C "Improvers" (those who experienced an AIS grade improvement) and "Non-Improvers" (No AIS change), and AIS grade A and D at <2 weeks ("Acute") and approx. 3 months ("Sub-acute") post-injury. The total protein concentration from each sample was extracted, with pooled samples being labelled and non-pooled samples treated with ProteoMiner beads. Samples were then analysed using two 4-plex isobaric tag for relative and absolute quantification (iTRAQ) analyses and a label-free experiment for comparison, before quantifying with mass spectrometry. Data are available via ProteomeXchange with identifiers PXD035025 and PXD035072 for the iTRAQ and label-free experiments respectively. Proteomic datasets were analysed using OpenMS (version 2.6.0). R (version 4.1.4) and in particular, the R packages MSstats (version 4.0.1) and pathview (version 1.32.0) were used for downstream analysis. Proteins of interest identified from this analysis were further validated by enzyme-linked immunosorbent assay (ELISA). 1.3. ResultsThe data demonstrated proteomic differences between the cohorts, with the results from the iTRAQ approach supporting those of the label-free analysis. A total of 79 and 87 differentially abundant proteins across AIS and longitudinal groups were identified from the iTRAQ and label-free analyses, respectively. Alpha-2-macroglobulin (A2M), retinol binding protein 4 (RBP4), serum amyloid A1 (SAA1), Peroxiredoxin 2, Apolipoprotein A1 (ApoA1) and several immunoglobulins were identified as bio-logically relevant and differentially abundant, with potential as individual prognostic biomarkers of neurological outcome. Bioinformatics analyses revealed that the majority of differentially abundant proteins were components of the complement cascade and most interacted directly with the liver. 1.4. ConclusionsMany of the proteins of interest identified using proteomics were detected only in a single group and therefore have potential as a binary (present or absent) biomarkers, RBP4 and PRX-2 in particular. Additional investigations into the chronology of these proteins, and their levels in other tissues (cerebrospinal fluid in particular) are needed to better understand the underlying pathophysiology, including any potentially modifiable targets. Pathway analysis highlighted the complement cascade as being significant across groups of differential functional recovery.

bioinformatics↗

bioRxiv2021

Treatment of infection-induced vascular pathologies is protective against persistent rough morphotype Mycobacterium abscessus infection in zebrafish

Mycobacterium abscessus infections are of increasing global prevalence and are often difficult to treat due to complex antibiotic resistance profiles. While there are similarities between the pathogenesis of M. abscessus and tuberculous mycobacteria, including granuloma formation and stromal remodeling, there are distinct molecular differences at the host-pathogen interface. Here we have used a zebrafish-M. abscessus model and host-directed therapies that were previously identified in the zebrafish-M. marinum model to identify potential host-directed therapies against M. abscessus infection. We find efficacy of anti-angiogenic and vascular normalizing therapies against rough M. abscessus infection, but no effect of anti-platelet drugs.

microbiology↗

bioRxiv2021

Infection-induced miR-126 suppresses tsc1- and cxcl12a-dependent permissive macrophages during mycobacterial infection

Regulation of host microRNA (miRNA) expression is a contested node that controls the host immune response to mycobacterial infection. The host must overcome concerted subversive efforts of pathogenic mycobacteria to launch and maintain a protective immune response. Here we examine the role of miR-126 in the zebrafish model of Mycobacterium marinum infection and identify a protective role for this infection-induced miRNA through multiple effector pathways. Specifically, we analyse the impact of the miR-126 knockdown-induced tsc1a and cxcl12a/ccl2/ccr2 signalling axes during early host-M. marinum interactions. We find a strong detrimental effect of tsc1a upregulation that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death despite dramatically higher recruitment of macrophages to the site of infection. We demonstrate that infection-induced miR-126 suppresses tsc1 and cxcl12a expression thus improving macrophage function early in infection, partially through activation of mTOR signalling and strongly through preventing the recruitment of Ccr2+ permissive macrophages, resulting in the recruitment of protective tnfa-expressing macrophages. Together our results demonstrate an important role for infection-induced miR-126 in shaping an effective immune response to M. marinum infection in zebrafish embryos.

immunology↗

bioRxiv2021

Exposure to the gut microbiota from cigarette smoke-exposed mice exacerbates cigarette smoke extract-induced inflammation in zebrafish larvae

Cigarette smoke (CS)-induced inflammation leads to a range of diseases including chronic obstructive pulmonary disease and cancer. The gut microbiota is a major modifying environmental factor that determine the severity of cigarette smoke-induced pathology. Microbiomes and metabolites from CS-exposed mice exacerbate lung inflammation via the gut-lung axis of shared mucosal immunity in mice but these systems are expensive to establish and analyse. Zebrafish embryos and larvae have been used to model the effects of cigarette smoking on a range of physiological processes and offer an amenable platform for screening modifiers of cigarette smoke-induced pathologies with key features of low cost and rapid visual readouts. Here we exposed zebrafish larvae to cigarette smoke extract (CSE) and characterised a CSE-induced leukocytic inflammatory phenotype with increased neutrophilic and macrophage inflammation in the gut. The CSE-induced phenotype was exacerbated by co-exposure to microbiota from the faeces of CS-exposed mice, but not control mice. Microbiota could be recovered from the gut of zebrafish and studied in isolation in a screening setting. This demonstrates the utility of the zebrafish-CSE exposure platform for identifying environmental modifiers of cigarette smoking-associated pathology and demonstrates that the CS-exposed mouse gut microbiota potentiates the inflammatory effects of CSE across host species.

immunology↗

bioRxiv2021

The role of L-arabinose metabolism for Escherichia coli O157:H7 in edible plants

Arabinose is a major plant aldopentose in the form of arabinans complexed in cell wall polysaccharides or glycoproteins (AGP), but comparatively rare as a monosaccharide. L-arabinose is an important bacterial metabolite, accessed by pectolytic microorganisms such as Pectobacterium atrosepticum via pectin and hemicellulose degrading enzymes. However, not all plant-associated microbes encode cell wall degrading enzymes, yet can metabolise L-arabinose, raising questions about their use of and access to the glycan in plants. Therefore, we examined L-arabinose metabolism in the food-borne pathogen Escherichia coli O157:H7 (isolate Sakai) during its colonisation of plants. L-arabinose metabolism (araBA) and transport (araF) genes were activated at 18 {degrees}C in vitro by L-arabinose and expressed over prolonged periods in planta. Although deletion of araBAD did not impact the colonisation ability of E. coli O157:H7 (Sakai) on plants, araA was induced on exposure to spinach cell wall polysaccharides. Furthermore, debranched and arabinan oligosaccharides induced ara metabolism gene expression in vitro, and stimulated modest proliferation, while immobilised pectin did not. Thus, E. coli O157:H7 (Sakai) can utilise pectin/AGP- derived L-arabinose as a metabolite, but differs fundamentally in ara gene organisation, transport and regulation from the related pectinolytic species P. atrosepticum, reflective of distinct plant- associated lifestyles.

microbiology↗

bioRxiv2020

Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis

Pathogenic mycobacteria actively dysregulate protective host immune signalling pathways during infection to drive the formation of permissive granuloma microenvironments. Dynamic regulation of host microRNA (miRNA) expression is a conserved feature of mycobacterial infections across host-pathogen pairings. Here we examine the role of miR-206 in the zebrafish model of Mycobacterium marinum infection, which allows investigation of the early stages of granuloma formation. We find miR-206 is upregulated following infection by pathogenic M. marinum and that antagomir-mediated knockdown of miR-206 is protective against infection. We observed striking upregulation of cxcl12a and cxcr4b in infected miR-206 knockdown zebrafish embryos and live imaging revealed enhanced recruitment of neutrophils to sites of infection. We used Crispr/Cas9-mediated knockdown of cxcl12a and cxcr4b expression and AMD3100 inhibition of Cxcr4 to show that the enhanced neutrophil response and reduced bacterial burden caused by miR-206 knockdown was dependent on the Cxcl12/Cxcr4 signalling axis. Together, our data illustrate a pathway through which pathogenic mycobacteria induce host miR-206 expression to suppress Cxcl12/Cxcr4 signalling and prevent protective neutrophil recruitment to granulomas. Author summaryMycobacterial infections cause significant disease burden to humans and animals, the most widely known example being tuberculosis which has killed more humans than any other infectious disease throughout history. Infectious mycobacteria are highly evolved to hijack host processes, including the very immune cells tasked with destroying them. microRNAs are host molecules that control wide-ranging programs of host gene expression and are important in the immune response to infections. Here we use the zebrafish model of mycobacterial infection to determine the role of the infection-induced microRNA miR-206 in the host response to infection. We found pathogenic mycobacteria trigger the host to produce more miR-206 in order to suppress the otherwise protective recruitment of neutrophils to sites of infection via the host Cxcl12/Cxcr4 signalling pathway. Our study provides new insight into the role of mycobacterial infection-induced miR-206 function in the context of a whole host.

immunology↗

bioRxiv2020

Foot shock facilitates reward seeking in an experience-dependent manner

Animals organize reward seeking around aversive events. An abundance of research shows that foot shock, as well as a shock-associated cue, can elicit freezing and suppress reward seeking. Yet, there is evidence that experience can flip the effect of foot shock to facilitate reward seeking. Here we examine cue suppression, foot shock suppression and foot shock facilitation of reward seeking in a single behavioural setting. Male Long Evans rats received fear discrimination consisting of danger, uncertainty and safety cues. Discrimination took place over a baseline of rewarded nose poking. With limited experience, all cues and foot shock strongly suppressed reward seeking. With continued experience, suppression became specific to shock-associated cues and foot shock facilitated reward seeking. Our results provide a means of assessing positive properties of foot shock, and may provide insight into maladaptive behavior around aversive events.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2019

Hot and sick: impacts of warming and oomycete parasite infection on endemic dominant zooplankter of Lake Baikal.

Climate warming impacts ecosystems through multiple interacting pathways, including via direct thermal responses of individual taxa and the combined responses of closely interacting species. In this study we examined how warming and infection by an oomycete parasite affect the dominant zooplankter of Russias Lake Baikal, the endemic cold-adapted stenotherm Epischura baikalensis (Copepoda). We used a combination of laboratory experiments, long-term monitoring data and population modeling. Experiments showed large thermal mismatch between host and parasite, with strong negative effects of warm temperatures on E. baikalensis survival and reproduction and a negative synergistic effect of Saprolegnia infection. However, Saprolegnia infection had an unexpected positive effect on E. baikalensis reproductive output, which may be consistent with fecundity compensation by infected females. Long-term monitoring data showed that Saprolegnia infections were most common during the warmest periods of the year and that infected individuals tended to accumulate in deep water. Population models, parameterized with experimental and literature data, correctly predicted the timing of Saprolegnia epizootics, but overestimated the negative effect of warming on E.baikalensis populations. Models suggest that diel vertical migration may allow E. baikalensis to escape the negative effects of increasing temperatures and parasitism and enable E. baikalensis to persist as Lake Baikal warms. Our results contribute to understanding of how multiple interacting stressors affect warming pelagic ecosystems of cold lakes and oceans and show that the population-level consequences of thermal mismatch between hosts and parasites can vary seasonally, interannual and spatially.

ecology↗