Biology subjects

Dale, J.

Publications and source records attributed to Dale, J..

9 recordsLinked to original sources

bioRxiv2024

Up-regulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain

Mitochondria and lysosomes are two organelles that carry out both signaling and metabolic roles in the cells. Recent evidence has shown that mitochondria and lysosomes are dependent on one another, as primary defects in one cause secondary defects in the other. Nevertheless, the signaling consequences of primary mitochondrial malfunction and of primary lysosomal defects are not similar, despite in both cases there are impairments of mitochondria and of lysosomes. Here, we used RNA sequencing to obtain transcriptomes from cells with primary mitochondrial or lysosomal defects, to identify what are the global cellular consequences that are associated with malfunction of mitochondria or lysosomes. We used these data to determine what are the pathways that are affected by defects in both organelles, which revealed a prominent role for the cholesterol synthesis pathway. This pathway is transcriptionally up-regulated in cellular and mouse models of lysosomal defects and is transcriptionally down-regulated in cellular and mouse models of mitochondrial defects. We identified a role for post-transcriptional regulation of the transcription factor SREBF1, a master regulator of cholesterol and lipid biosynthesis, in models of mitochondrial respiratory chain deficiency. Furthermore, the retention of Ca2+ in the lysosomes of cells with mitochondrial respiratory chain defects contributes to the differential regulation of the cholesterol synthesis pathway in the mitochondrial and lysosomal defects tested. Finally, we verified in vivo, using models of mitochondria-associated diseases in C. elegans, that normalization of lysosomal Ca2+ levels results in partial rescue of the developmental arrest induced by the respiratory chain deficiency.

biochemistry↗

bioRxiv2023

Social and environmental transmission spread different sets of gut microbes in wild mice

Gut microbes shape many aspects of organismal biology, yet how these key bacteria transmit among hosts in natural populations remains poorly understood. Recent work in mammals has emphasized either transmission through social contacts or indirect transmission through environmental contact, but the relative importance of different routes has not been directly assessed. Here, we used a novel RFID-based tracking system to collect long-term high resolution data on social relationships, space use and microhabitat in a wild population of mice (Apodemus sylvaticus), while regularly characterising their gut microbiota. Through probabilistic modelling of the resulting data, we identify positive and statistically distinct signals of social and environmental transmission, captured by social networks and overlap in home ranges respectively. Strikingly, microbes with distinct biological attributes drove these different transmission signals. While aerotolerant spore-forming bacteria drove the effect of shared space use, a mix of taxa but especially anaerobic bacteria underpinned the social networks effect on gut microbiota similarity. These findings provide the first evidence for parallel social and environmental transmission of gut microbes that involve biologically distinct subsets of the mammalian gut microbiota. List of contributionsO_LIAura Raulo designed the study, helped develop the new RFID tracking technology, collected the data from Wytham, completed all laboratory analyses on gut microbiota profiling prior to sequencing, developed analytical methods, analysed the data and wrote the manuscript C_LIO_LIPaul Burkner helped design the Bayesian probabilistic modeling framework and provided feedback on the manuscript C_LIO_LIJarrah Dale helped collect field data using RFID loggers C_LIO_LIHolly English helped collect field data using RFID loggers and provided feedback on home range analyses C_LIO_LIGenevieve Finerty helped with home range analysis and the analysis of microhabitat variation and provided feedback on the manuscript C_LIO_LICurt Lamberth led development of RFID tracking devices and helped collect field data from Wytham C_LIO_LIJosh Firth supervised the research project, developed social network analysis methods and provided feedback on the analyses and the manuscript C_LIO_LITim Coulson supervised the research project and provided feedback on the analyses and the manuscript C_LIO_LISarah Knowles supervised the research project, helped develop the tracking technology and design the study, collected data from Wytham, planned and supervised laboratory methods, developed analytical methods and provided feedback on analyses and the manuscript. C_LI

ecology↗

bioRxiv2023

Investigating a Gulf Stream Frontal Eddy North of Cape Hatteras: Questioning Overall Impacts on Ecology

Ocean physics and biology can interact in myriad and complex ways. Eddies, features found at many scales in the ocean, can drive substantial changes in physical and biogeochemical fields with major implications for marine ecosystems. Mesoscale eddies are challenging to model and difficult to observe synoptically at sea due to their fine-scale variability yet broad extent. In this work we observed a frontal eddy just north of Cape Hatteras via an intensive hydrographic, biogeochemical, and optical sampling campaign. Frontal eddies occur in western boundary currents around the globe and there are major gaps in our understanding of their ecosystem impacts. In the Gulf Stream, frontal eddies have been studied in the South Atlantic Bight, where they are generally assumed to shear apart passing Cape Hatteras. However, we found that the observed frontal eddy had different physical properties and phytoplankton community composition from adjacent water masses, in addition to continued cyclonic rotation. In this work we first synthesize the overall ecological impacts of frontal eddies in a simple conceptual model. This conceptual model led to the hypothesis that frontal eddies could be well timed to supply zooplankton to secondary consumers off Cape Hatteras where there is a notably high concentration and diversity of top predators. Towards testing this hypothesis and our conceptual model we report on the biogeochemical state of this particular eddy connecting physical and biological dynamics, analyze how it differs from Gulf Stream and shelf waters even in "death", and refine our initial model with this new data. Key PointsO_LIIn-depth investigation of a frontal eddy in the Gulf Stream off Cape Hatteras, North Carolina C_LIO_LIContinued physical and biogeochemical differences are observed between the eddy and adjacent water masses even as it begins to shear apart C_LIO_LIWe share a conceptual model of the ecological impact of frontal eddies with a hypothesis that they supply zooplankton to secondary consumers C_LI Plain Language SummaryFrontal eddies are spinning masses of water (~30km in diameter) that move along western boundary currents like the Gulf Stream. When they form they carry productive coastal water into the Gulf Stream and drive upwelling within their cores. Together this leads to an increase in the amount of phytoplankton within them - much higher compared to surrounding nutrient-limited Gulf Stream water. On the east coast of the United States one common area of frontal eddy formation is just off Charleston, SC. Eddies then travel up the coast and dissipate near Cape Hatteras, NC. In this work we measured a wide range of physical and biological properties of a frontal eddy just north of Cape Hatteras. We compared these properties within the eddy to the coastal water on one side and the Gulf Stream water on the other, finding clear differences in phytoplankton community composition and other physical and chemical properties. Using the results of these observations together with previous studies we share a simple model for how frontal eddies may impact phytoplankton, zooplankton, and fish - hypothesizing that they may contribute to the high diversity and density of top predators off Cape Hatteras.

ecology↗

bioRxiv2021

Bridging functional annotation gaps in non-model plant genes with AlphaFold, DeepFRI and small molecule docking

BackgroundFunctional annotation assigns descriptive biological meaning to genetic sequences. Limited availability of manually curated or experimentally validated plant genes from a diverse range of taxa poses a significant challenge for functional annotation in non-model organisms. Accurate computational approaches are required. We argue that recent breakthroughs in deep learning have the potential to not only narrow the functional annotation gap between non-model and model plant organisms, but also annotate and reveal novel functions even for genes with no homologs in public databases. ResultsDeep learning models were applied to functionally annotate a set of previously published differentially expressed genes. Predicted protein structures and functional annotations were generated using the AlphaFold protein structure and DeepFRI protein language inference models respectively. The resulting structures and functional annotations were validated using small molecule docking experiments. DeepFRI and AlphaFold models not only correctly annotated differentially expressed genes, but also revealed detailed mechanisms involving protein-protein interactions. ConclusionsDeep learning models are capable of inferring novel functions and achieving high accuracy in functional annotation. Their increased use in plant research will result in major improvements in annotations for non-model plants that are underrepresented in genome databases. We illustrate how integrating protein structure prediction, functional residue prediction, and small molecule docking can infer plausible protein-protein interactions and yield additional mechanistic insights. This approach will aid in the selection of candidate genes for further study from differential expression studies that generate large gene lists.

bioinformatics↗

bioRxiv2021

Long read sequencing reveals atypical mitochondrial genome structure in a New Zealand marine isopod

Most animal mitochondrial genomes are small, circular, and structurally conserved. However, recent work indicates that diverse taxa possess unusual mitochondrial genomes. In Isopoda, species in multiple lineages have atypical and rearranged mitochondrial genomes. However, more species of this speciose taxon need to be evaluated to understand the evolutionary origins of atypical mitochondrial genomes in this group. In this study, we report the presence of an atypical mitochondrial structure in the New Zealand endemic marine isopod, Isocladus armatus. Data from long and short read DNA sequencing, suggests that I. armatus has two mitochondrial chromosomes. The first chromosome consists of two mitochondrial genomes that have been inverted and fused together in a circular form, and the second chromosome consists of a single mitochondrial genome in a linearized form. This atypical mitochondrial structure has been detected in other isopod lineages, and our data from an additional divergent isopod lineage (Sphaeromatidae) lends support to the hypothesis that atypical structure evolved early in the evolution of Isopoda. Additionally, we find that a heteroplasmic site previously observed across many species within Isopoda is absent in I. armatus, but confirm the presence of two heteroplasmic sites recently reported in two other isopod species.

genomics↗

bioRxiv2021

Inferring Mycobacterium bovis transmission between cattle and badgers using isolates from the Randomised Badger Culling Trial

Mycobacterium bovis (M. bovis) is a causative agent of bovine tuberculosis, a significant source of morbidity and mortality in the global cattle industry. The Randomised Badger Culling Trial was a field experiment carried out between 1998 and 2005 in the South West of England. As part of this trial, M. bovis isolates were collected from contemporaneous and overlapping populations of badgers and cattle within ten defined trial areas. We combined whole genome sequences from 1,442 isolates with location and cattle movement data, identifying transmission clusters and inferred rates and routes of transmission of M. bovis. Most trial areas contained a single transmission cluster that had been established shortly before sampling, often contemporaneous with the expansion of bovine tuberculosis in the 1980s. The estimated rate of transmission from badger to cattle was approximately two times higher than from cattle to badger, and the rate of within-species transmission considerably exceeded these for both species. We identified long distance transmission events linked to cattle movement, recurrence of herd breakdown by infection within the same transmission clusters and superspreader events driven by cattle but not badgers. Overall, our data suggests that the transmission clusters in different parts of South West England that are still evident today were established by long-distance seeding events involving cattle movement, not by recrudescence from a long-established wildlife reservoir. Clusters are maintained primarily by within-species transmission, with less frequent spill-over both from badger to cattle and cattle to badger.

genomics↗

bioRxiv2020

Population Structure in a Direct-Developing Marine Isopod

Marine organisms generally exhibit one of two developmental modes: biphasic, with distinct adult and larval morphology, and direct development, in which larvae resemble adults. Developmental mode is thought to significantly influence dispersal, with direct developers expected to have much lower dispersal potential. However, in contrast to our relatively good understanding of dispersal and population connectivity for biphasic species, comparatively little is known about direct developers. In this study, we use a panel of 8,020 SNPs to investigate population structure and gene flow for a direct developing species, the New Zealand endemic marine isopod Isocladus armatus. On a small spatial scale (20 kms), gene flow between locations is extremely high and suggests an island model of migration. However, over larger spatial scales (600km), populations exhibit a clear pattern of isolation-by-distance. Because our sampling range is intersected by two well-known biogeographic barriers (the East Cape and the Cook Strait), our study provides an opportunity to understand how such barriers influence dispersal in direct developers. Our results indicate that I. armatus exhibits significant migration across these barriers, and suggests that ocean currents associated with these locations do not present a barrier to dispersal. Interestingly, we do find evidence of a north-south population genetic break occurring between M[a]hia and Wellington, two locations where there are no obvious biogeographic barriers between them. We conclude that developmental life history largely predicts dispersal in intertidal marine isopods. However, localised biogeographic processes can disrupt this expectation.

ecology↗

bioRxiv2018

RECONCILING ECOGEOGRAPHICAL RULES: RAINFALL AND TEMPERATURE PREDICT GLOBAL COLOUR VARIATION IN THE LARGEST BIRD RADIATION

Ecogeographical rules that associate climate with organismal form and function can reveal patterns of climatic adaptation. Two rules link animal coloration with climate: Glogers rule (darker coloration where wet and warm), and Bogerts rule (darker coloration where cold). Whereas Glogers rule was proposed for endotherms, and Bogerts rule for ectotherms, both rules may apply more broadly, despite their seemingly opposing effects. Here we test this contradiction on a global scale across passerine birds. Consistent with Glogers rule, birds were darker in wetter areas and, following Bogerts rule, lighter where warm, although birds became lighter again at very low temperatures. Rainfall and temperature had antagonistic or additive effects depending on their pattern of covariation, and this predicted whether birds followed the rules. We integrate both rules into a general framework to explain heterogeneity in climatic effects on coloration, which has implications to understand patterns of diversification, climatic adaptation and climate change impacts.

evolutionary biology↗

bioRxiv2018

New tools for diet analyses: nanopore sequencing of metagenomic DNA from stomach contents to quantify diet in an invasive population of rats

BackgroundUsing metagenomics to determine animal diet offers a new and promising alternative to current methods. Here we show that rapid and inexpensive diet quantification is possible through metagenomic sequencing with the portable Oxford Nanopore Technologies (ONT) MinION. Using an amplification-free approach, we profiled the stomach contents from wild-caught rats. ResultsWe conservatively identified diet items from over 50 taxonomic orders, ranging across nine phyla that include plants, vertebrates, invertebrates, and fungi. This highlights the wide range of taxa that can be identified using this simple approach. We calibrate the accuracy of this method by comparing the characteristics of reads matching the ground-truth host genome (rat) to those matching diet items, and show that at the family-level, false positive taxon assignments are approximately 97.5% accurate. We also suggest a way to mitigate for database biases in metagenomic approaches. Finally, we implement a constrained ordination analysis and show that we can identify the sampling location of an individual rat within tens of kilometres based on diet content alone. ConclusionsThis work establishes proof-of-principle for long-read metagenomic methods in quantitative diet analysis. We show that diet content can be quantified even with limited expertise, using a simple, amplification free workflow and a relatively inexpensive and accessible next generation sequencing method. Continued increases in the accuracy and throughput of ONT sequencing, along with improved genomic databases, suggests that a metagenomic approach to quantification of animal diets will become an important method in the future.

ecology↗