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Bury, N. R.

Publications and source records attributed to Bury, N. R..

3 recordsLinked to original sources

Developmental priming increases copper-tolerance in a model fish species via epigenetic-and microbiome-mediated mechanisms

Pollution is a significant threat to aquatic ecosystems globally and, in order to survive, natural populations depend upon their ability to rapidly develop tolerance to chemical stressors. We examined whether early-life priming enhances life-long copper-tolerance in a model fish species via developmental plasticity. Stickleback (Gasterosteus aculeatus) embryos were pre-exposed to a low concentration of copper (10 {micro}g/L) during early development, reared in clean water for nine months alongside a control group, and then exposed to copper (0,10 and 20 {micro}g/L) for 96 h as adults. Priming markedly reduced evidence of copper-toxicity in adult gills at the transcriptional level (including reduced cellular stress response (CSR) and disruption of ion-homeostasis) and increased inducibility of the metal-binding protein, metallothionein. In parallel, we identified epigenetic and microbiome-mediated mechanisms likely contributing to this tolerance. Pre-exposure induced persistent DNA methylation changes, consistent with priming of CSR and ion-homeostasis pathways. We identified enhanced copper-tolerance in the gill microbiota of primed fish that likely also contributed to host tolerance. These findings provide critical evidence for developmental plasticity induced by chemical stressors in animals, highlight the importance of integrated microbiome and epigenetic responses, and enhance our understanding of how natural populations cope with pollution in their environment.

evolutionary biology↗

Binding Affinity Ranking at the Molecular Initiating Event (BARMIE): An open-source computational pipeline for ecological hazard ranking of endocrine disrupting chemicals.

A challenge in ecological risk assessment is identifying the chemicals that pose the greatest threat and determining which species are most vulnerable to them. To help address this, this study has developed an in-silico open-source tool called BARMIE (Binding Affinity Ranking at the Molecular Initiating Event) to rapidly predict the chemical binding affinity of steroid receptor proteins to synthetic steroids to identify potentially vulnerable species and chemicals of concern. BARMIE was used to screen 163 teleost fish glucocorticoid receptors (GRs) for binding to the natural ligand cortisol and to 10 synthetic glucocorticoid drugs (GCs) designed to interact within the ligand-binding pocket (LBP) of GRs. BARMIE identified species from the superorder Protacanthopterygii with high-affinity GRs to synthetic GCs (e.g. vulnerable species). . BARMIE was also used to screen binding profiles of compounds in the Medicine for Malaria Venture Global Health Priority Box to rainbow trout GRs (rtGR1 and rtGR2). Of the 178 compounds, 24 and 36 bind within the LBP of rtGR1 and rtGR2, respectively. For 30 of these compounds, transactivation activity was assessed at 1{micro}M in the presence or absence of 1{micro}M cortisol and confirmed 2 compounds with agonistic properties (e.g. chemicals of concern) that would require further in vitro and/or in vivo studies to assess the environmental risk. BARMIE can rapidly generate predicted binding affinities for 100s of species and chemicals as a first screen in environmental risk assessment to provide information on which substances to prioritise in downstream tests.

pharmacology and toxicology↗

Combining population genomics and transcriptomics to identify signatures of metal tolerance in brown trout inhabiting metal-polluted rivers

Industrial pollution is a major driver of ecosystem degradation, but it can also act as a driver of contemporary evolution. As a result of intense mining activity during the Industrial Revolution, several rivers across the southwest of England are polluted with high concentrations of metals. Despite the documented negative impacts of ongoing metal pollution, brown trout (Salmo trutta L.) survive and thrive in many of these metal-impacted rivers. We used population genomics, transcriptomics, and metal burdens to investigate the genomic and transcriptomic signatures of potential metal tolerance. RADseq analysis of six populations (originating from three metal-impacted and three control rivers) revealed strong genetic substructuring between impacted and control populations. We identified selection signatures at 122 loci, including genes related to metal homeostasis and oxidative stress. Trout sampled from metal-impacted rivers exhibited significantly higher tissue concentrations of cadmium, copper, nickel, and zinc, which remained elevated after 11 days in metal-free water. After depuration, we used RNAseq to quantify gene expression differences between metal-impacted and control trout, identifying 2,042 differentially expressed genes (DEGs) in the gill, and 311 DEGs in the liver. Transcriptomic signatures in the gill were enriched for genes involved in ion transport processes, metal homeostasis, oxidative stress, hypoxia and response to xenobiotics. Our findings reveal shared genomic and transcriptomic pathways involved in detoxification, oxidative stress responses, and ion regulation. Overall, our results demonstrate the diverse effects of metal pollution in shaping both neutral and adaptive genetic variation, whilst also highlighting the potential role of constitutive gene expression in promoting metal tolerance.

evolutionary biology↗