Biology subjects

Pope, B.

Publications and source records attributed to Pope, B..

8 recordsLinked to original sources

bioRxiv2026

A mosaic of genomic architectures underpins parasitism loss in a jawless vertebrate

Lampreys are the only ancestrally parasitic vertebrate lineage, yet parasitism has been repeatedly lost alongside a suite of life-history changes, such as loss of migration and juvenile feeding and accelerated maturation. Combining whole-genome resequencing, haplotype-resolved assemblies, hybrid-zone genotyping, multi-tissue transcriptomics, and sperm phenotyping, we map this life-history syndrome in European Lampetra to six chromosomes spanning a mosaic of genomic architectures: a [~]20 Mb low-recombination region on chromosome 1 lacking chromosomal rearrangements within Lampetra but involving inter-specific rearrangements across deep lamprey lineages; a translocated inversion with ecotype-dependent sperm-velocity effects; and ecotype-divergent deletions overlapping genes crucial for nervous system (CNTNAP2) and reproductive development (FSHR). However, this genomic basis is not shared with a convergent sister lineage, pointing to independent routes to a recurring life-history transition in lampreys.

evolutionary biology↗

bioRxiv2024

Role of vaccinia virus growth factor in stimulating the mTORC1-CAD axis of the de novo pyrimidine pathway under different nutritional cues

Vaccinia virus (VACV), the prototype poxvirus, actively reprograms host cell metabolism upon infection. However, the nature and molecular mechanisms remain largely elusive. Given the diverse nutritional exposures of cells in different physiological contexts, it is essential to understand how VACV may alter various metabolic pathways in different nutritional conditions. In this study, we established the importance of de novo pyrimidine biosynthesis in VACV infection. We elucidated the significance of vaccinia growth factor (VGF), a viral early protein and a homolog of cellular epidermal growth factor, in enabling VACV to phosphorylate the key enzyme CAD of the de novo pyrimidine pathway at serine 1859, a site known to positively regulate CAD activity. While nutrient-poor conditions typically inhibit mTORC1 activation, VACV activates CAD via mTORC1-S6K1 signaling axis, in conditions where glutamine and asparagine are absent. However, unlike its cellular homolog, epidermal growth factor (EGF), VGF peptide alone in the absence of VACV infection has minimal ability to activate CAD, suggestive of the involvement of other viral factor(s) and differential functions to EGF acquired during poxvirus evolution. Our research provides a foundation for understanding the regulation of a significant metabolic pathway, namely, de novo pyrimidine synthesis during VACV infection, shedding new light on viral regulation under distinct nutritional environments. This study not only has the potential to contribute to the advancement of antiviral treatments but also improve the development of VACV as an oncolytic agent and vaccine vector. ImportanceOur research provides new insights into how VACV alters the mTORC1-CAD signaling axis under different nutritional cues. The identification of how VACV regulates a major enzyme, CAD, within the de novo pyrimidine synthesis pathway, establishes a molecular mechanism for determining how VACV reshapes this essential pathway, necessary for facilitating efficient VACV replication. We further emphasize that, despite nutrient-poor conditions, which typically inhibit mTORC1 activation, VACV can stimulate mTORC1. We identify its early growth factor, VGF, as an important factor for this stimulation of mTORC1 and its downstream effector CAD, revealing a new mechanism for how VACV sustains mTORC1-CAD axis activation under these nutrient deficient conditions. This work provides fresh insights into the molecular mechanisms of mTORC1-CAD regulation, which has the potential to be utilized to enhance VACV as an oncolytic tool, vaccine vector and aid in the development of antiviral drugs.

microbiology↗

bioRxiv2024

Reproductive modes of polyploid Ludwigia grandiflora subsp. hexapetala in western Europe: the effects of a late-acting self-incompatibility system and its absence on genetic diversity within populations

Reproductive mode, i.e., the proportion of individuals produced by clonality, selfing and outcrossing in populations, determines how hereditary material is transmitted through generations. It shapes genetic diversity and its structure over time and space, which can be used to infer reproductive modes. Ludwigia grandiflora subsp. hexapetala (Lgh) is a partially clonal, polyploid, hermaphroditic, and heteromorphic plant that recently colonized multiple countries worldwide. In western Europe, individuals are either self-incompatible caused by a late-acting self-incompatibility (LSI) system developing long-styled flowers, or self-compatible (SC), with short-styled flowers. In this study, we genotyped 53 long- and short-styled populations newly colonizing France and northern Spain using SNPs to estimate rates of clonality, selfing and outcrossing. We found that populations reproduced mainly clonally but with a high diversity of genotypes along with rates of sexuality ranging from 10% up to 40%. We also found evidence for local admixture between long- and short-styled populations in a background of genetic structure between floral morphs that was twice the level found within morphs. Long- and short-styled populations showed similar rates of clonality but short-styled populations presented significantly higher rates of selfing, as expected considering their breeding system, and despite the small rates of failure of the LSI system. Within the 53 studied populations, the 13 short-styled populations had fewer effective alleles, lower observed heterozygosity, and higher inbreeding coefficients, linkage disequilibrium and estimates of selfing than what was found in long-styled populations. These results emphasize the necessity to consider the variation of reproductive modes when managing invasive plant species. The overall maintenance of higher genetic diversity with the possibility of maintaining populations clonally in the absence of compatible partners may explain why long-styled individuals seem to be more prevalent in all newly expanding populations worldwide. Beyond Lgh, our methodological approach may inspire future studies to assess the reproductive modes in other autopolyploid populations.

evolutionary biology↗

bioRxiv2023

Antiviral activities of two nucleos(t)ide analogs against vaccinia and mpox viruses in primary human fibroblasts

Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox. Identification of inhibitors of poxvirus replication is critical for drug development to manage poxvirus threats. Here we tested two compounds, nucleoside trifluridine and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV) and mpox virus (MPXV) in physiologically relevant primary human fibroblasts. Both trifluridine and adefovir dipivoxil potently inhibited replication of VACV and MPXV (MA001 2022 isolate) in a plaque assay. Upon further characterization, they both conferred high potency in inhibiting VACV replication with half maximal effective concentrations (EC50) at low nanomolar levels in our recently developed assay based on a recombinant VACV secreted Gaussia luciferase. Our results further validated that the recombinant VACV with Gaussia luciferase secretion is a highly reliable, rapid, non-disruptive, and simple reporter tool for identification and chracterization of poxvirus inhibitors. Both compounds inhibited VACV DNA replication and downstream viral gene expression. Given that both compounds are FDA-approved drugs, and trifluridine is used to treat ocular vaccinia in medical practice due to its antiviral activity, our results suggest that it holds great promise to further test trifluridine and adefovir dipivoxil for countering poxvirus infection, including mpox.

microbiology↗

bioRxiv2021

VIVID: a web application for variant interpretation and visualisation in multidimensional analyses

Large-scale comparative genomics- and population genetic studies generate enormous amounts of polymorphism data in the form of DNA variants. Ultimately, the goal of many of these studies is to associate genetic variants to phenotypes or fitness. We introduce VIVID, an interactive, user-friendly web application that integrates a wide range of approaches for encoding genotypic to phenotypic information in any organism or disease, from an individual or population, in three-dimensional (3D) space. It allows mutation mapping and annotation, calculation of interactions and conservation scores, prediction of harmful effects, analysis of diversity and selection, and 3-dimensional (3D) visualisation of genotypic information encoded in Variant Call Format (VCF) on AlphaFold2 protein models. VIVID enables the rapid assessment of genes of interest in the study of adaptive evolution and the genetic load, and it helps prioritising targets for experimental validation. We demonstrate the utility of VIVID by exploring the evolutionary genetics of the parasitic protist Plasmodium falciparum, revealing geographic variation in the signature of balancing selection in potential targets of functional antibodies.

bioinformatics↗

bioRxiv2020

Genome Methylation Predicts Age and Longevity of Bats

Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.

genomics↗

bioRxiv2019

Corticosterone as a potential confounding factor in delineating mechanisms underlying ketamine's rapid antidepressant actions

Although ketamine represents a new line of antidepressants with unique clinical advantages, its use as a long-term treatment has limitations, particularly its dissociative/psychotomimetic effects and abuse potential. In rats, we observed that a subanesthetic dose of ketamine (10mg/kg) induced a 3-fold increase in corticosterone (CORT) levels in both serum and brain tissue, within an hour of administration. This increase took place in both male and female rats, in both naive and stressed animals. However, no CORT increase was detected in rats injected with (2R, 6R)-hydroxynorketamine (HNK), an active metabolite of ketamine, that is believed to contribute to ketamines antidepressant effect. In response to the release in CORT, ketamine injected animals displayed a significant increase in the expression of sgk1, a downstream effector of glucocorticoid receptor signaling, in the hippocampus indicating the initiation of a transcriptional program. We hypothesized this surge in CORT release was a manifestation of stress experienced by the rat in response to ketamines psychotropic effects. When sensory perception was blocked under isoflurane anesthesia, administration of ketamine did not increase circulating CORT levels as compared to animals injected with saline. Taken together, ketamine administration triggers a behavioral stress response that has downstream molecular consequences. The resulting CORT release, virtually concurrent with the timing of ketamines rapid-acting antidepressant actions, necessitates the consideration of this pathways potential involvement when trying to dissect out the relevant molecular mechanisms underlying ketamines action.

neuroscience↗

bioRxiv2017

Best Practice Data Life Cycle Approaches for the Life Sciences

Throughout history, the life sciences have been revolutionised by technological advances; in our era this is manifested by advances in instrumentation for data generation, and consequently researchers now routinely handle large amounts of heterogeneous data in digital formats. The simultaneous transitions towards biology as a data science and towards a life cycle view of research data pose new challenges. Researchers face a bewildering landscape of data management requirements, recommendations and regulations, without necessarily being able to access data management training or possessing a clear understanding of practical approaches that can assist in data management in their particular research domain.\n\nHere we provide an overview of best practice data life cycle approaches for researchers in the life sciences/bioinformatics space with a particular focus on omics datasets and computer-based data processing and analysis. We discuss the different stages of the data life cycle and provide practical suggestions for useful tools and resources to improve data management practices.

bioinformatics↗