Biology subjects

Ball, E.

Publications and source records attributed to Ball, E..

7 recordsLinked to original sources

bioRxiv2026

microRNA expression during early development in the coral Acropora digitifera

Acropora spp. are the dominant reef-builders of the Indo-Pacific but are also amongst the most stress-sensitive corals. For these reasons, Acropora spp. have become the most studied of corals, two species (A. digitifera and A. millepora) often essentially serving as the basis for understanding molecular responses and processes across the sub-order Refertina and corals in general. The early development of these species has been well-characterised in terms of morphology and gene expression but as yet we have a limited understanding of how transcription is regulated during development. In "higher" animals (bilaterians) microRNAs (miRNAs) are critical regulators of gene expression but until now their involvement in coral development has not been investigated. Building on the existing developmental data for Acropora spp., we catalogued microRNAs (miRNAs) expressed during the early development of Acropora digitifera and profiled their expression in 21 stages from unfertilised eggs to 24h after treatment with a natural settlement cue (CCA chips). 157 miRNAs were recognised, many of which ([~]60%) were novel. These fell into three distinct groups, corresponding to three distinct developmental phases: (1) those present in eggs through to gastrulation (2) a larvally expressed group and (3) those expressed following settlement induction. Exposure of competent larvae to a natural settlement inducer resulted in major changes in the miRNA profile within 10 minutes, indicating that miRNAs may be particularly important in mediating the larva/polyp transition but are also likely to play important regulatory roles throughout early coral development in addition to possible roles in disease resistance.

developmental biology↗

bioRxiv2026

t2pmhc: A Structure-Informed Graph Neural Network to predict TCR-pMHC Binding

Mapping of T cell receptors (TCRs) to their cognate MHC-presented peptides (pMHC) is central for the development of precision immunotherapies and vaccine design. However, accurate prediction of TCR affinity to peptide antigens remains an open challenge. Most approaches rely solely on sequence information, although increasing evidence suggests that TCR-pMHC binding is primarily determined by three-dimensional structural interactions within the entire TCR-pMHC complex. Consequently, sequence-based methods often fail to generalize to peptides not included in the training data (unseen peptides). Here we introduce t2pmhc, a structure-based graph neural network framework for predicting TCR-pMHC binding using predicted structures of the entire TCR-pMHC complex. We evaluated a Graph Convolutional Network (GCN) and a Graph Attention Network, both demonstrating improved generalization to unseen peptides compared to state-of-the-art models across a variety of public datasets. Evaluation with crystallographic structures yields high-confidence predictions, indicating that current limitations of structure-based models are largely driven by the accuracy of structure prediction. Analysis of node attention patterns in t2pmhc-GCN reveals biologically consistent patterns, assigning high attention to the peptide and the CDR3 regions. Within the peptide sequence, canonical MHC anchor residues are consistently downweighted, whereas potential TCR-binding residues are upweighted. These findings establish t2pmhc as a structure-informed framework for robust TCR-pMHC binding prediction, enabling improved generalization to unseen antigens and providing a foundation for integrating TCR repertoire sequencing into vaccine design and immunotherapy.

bioinformatics↗

bioRxiv2025

Comparative virulence analysis of seven diverse strains of Orientia tsutsugamushi reveals a multifaceted and complex interplay of virulence factors responsible for disease.

Orientia tsutsugamushi is an obligate intracellular bacterium found in Leptotrombidium mites that causes the human disease scrub typhus. A distinguishing feature of O. tsutsugamushi is its extensive strain diversity, yet differences in virulence between strains are not well defined nor well understood. We sought to determine the bacterial drivers of pathogenicity by comparing murine infections using seven strains combined with epidemiological human data to rank each strain in terms of relative virulence. Murine cytokine expression data revealed that the two most virulent strains, Ikeda and Kato, induced higher levels of IL-6, IL-10, IFN-{gamma} and MCP-1 than other strains, consistent with increased levels of these cytokines in severe human scrub typhus patients. We sought to identify the mechanistic basis of the observed differential virulence between strains by comparing their genomes, in vitro growth properties and cytokine/chemokine induction in host cells. We found that there was no single gene or gene group that correlated with virulence, and no clear pattern of in vitro growth rate that predicted disease. However, microscopy-based analysis of the intracellular infection cycle revealed that the only fully avirulent strain in our study, TA686, differed from all the virulent strains in its subcellular localisation and expression of its surface protein ScaC. We conclude that drivers of pathogenicity in Orientia tsutsugamushi are distributed throughout the genome, likely in the large and varying arsenal of effector proteins encoded by different strains, and that these interact in complex ways to induce differing immune responses and thus differing disease outcomes in mammalian hosts. Author SummaryScrub typhus is a vector-borne human disease caused by the bacterium Orientia tsutsugmushi and spread by mites. There are numerous different strains of this bacterium with some causing more severe disease in humans than others, and some that do not cause any illness at all. The factors driving these differences are not yet understood, and gaining insight into them could aid in vaccine development and help predict the severity of disease caused by new isolates. To better determine the mechanistic basis of pathogenicity in scrub typhus, we carried out experiments in which we compared seven diverse strains for virulence in animals. We measured their ability to cause disease in mice, so that we could reliably classify them as virulent or avirulent in this model. We then analysed various genomic and biological aspects to identify disease markers in both mice and humans. We report here that there is no single factor that predicts whether a strain will be pathogenic or not, but that disease in scrub typhus is a complex process resulting from the activity of multiple bacterial genes working together to drive different immune responses in the host, resulting in either clearance of the bacteria from the host, or escalating disease. Future work exploring the relationship of bacterial effector proteins will help to disentangle this complex relationship in mechanistic detail.

microbiology↗

bioRxiv2024

Open-source 3D printed manifolds for exposure studies using human airway epithelial cells

RationaleInhalation of airborne stimuli can damage the airway epithelium, increasing the risk of developing respiratory or systemic diseases. In vitro studies using air-liquid interface cell cultures enable controlled investigation of cellular responses to relevant exposures. Commercial in vitro exposure systems provide precise and reproducible dosage but require significant capital investment and are not amenable to customization. Research groups interested in respiratory exposure science may benefit from a more accessible alternative open-source exposure system. We present 3D printed manifolds for applying a range of airborne exposures uniformly across standard, commercially available 6- and 24-well plates with air-liquid interface culture inserts. MethodsA simple chamber-style exposure system and the manifolds were evaluated for exposure uniformity via computational fluid dynamics simulations and deposition of nebulized FITC-labelled dextran. The chamber and manifolds were manufactured using a stereolithography 3D printer. Cannabis concentrate vapor was generated from 3 different vaporizers and applied to well plates using the manifold system. Calu-3 cells were cultured on Transwell inserts and exposed to whole tobacco smoke or room air. ResultsThe manifolds produced less variation in simulated air velocities and physical deposition of FITC-dextran aerosol deposition across well plates compared to those of the chamber-style exposure system. Distinct doses of cannabis concentrate vapour were delivered to well plates with low variation among wells. Whole tobacco smoke exposure using the manifold system induced functional changes in Calu-3 airway epithelial cell barrier function, cytokine production (IL-6 and IL-8), and cell membrane potential. ConclusionsCollectively, our data demonstrate the feasibility and the validity of our open-source 3D printed manifolds for use in studying various respiratory exposures and position our designs as more accessible options in parallel with commercially available systems. All article content is licensed under a Creative Commons Attribution (CC BY-NC 4.0) license (https://creativecommons.org/licenses/by-nc/4.0/).

bioengineering↗

bioRxiv2021

The B.1.427/1.429 (epsilon) SARS-CoV-2 variants are more virulent than ancestral B.1 (614G) in Syrian hamsters

As novel SARS-CoV-2 variants continue to emerge, it is critical that their potential to cause severe disease and evade vaccine-induced immunity is rapidly assessed in humans and studied in animal models. In early January 2021, a novel variant of concern (VOC) designated B.1.429 comprising 2 lineages, B.1.427 and B.1.429, was originally detected in California (CA) and shown to enhance infectivity in vitro and decrease antibody neutralization by plasma from convalescent patients and vaccine recipients. Here we examine the virulence, transmissibility, and susceptibility to pre-existing immunity for B 1.427 and B 1.429 in the Syrian hamster model. We find that both strains exhibit enhanced virulence as measured by increased body weight loss compared to hamsters infected with ancestral B.1 (614G), with B.1.429 causing the most body weight loss among all 3 lineages. Faster dissemination from airways to parenchyma and more severe lung pathology at both early and late stages were also observed with B.1.429 infections relative to B.1. (614G) and B.1.427 infections. In addition, subgenomic viral RNA (sgRNA) levels were highest in oral swabs of hamsters infected with B.1.429, however sgRNA levels in lungs were similar in all three strains. This demonstrates that B.1.429 replicates to higher levels than ancestral B.1 (614G) or B.1.427 in the upper respiratory tract (URT) but not in the lungs. In multi-virus in-vivo competition experiments, we found that epsilon (B.1.427/B.1.429) and gamma (P.1) dramatically outcompete alpha (B.1.1.7), beta (B.1.351) and zeta (P.2) in the lungs. In the URT gamma, and epsilon dominate, but the highly infectious alpha variant also maintains a moderate size niche. We did not observe significant differences in airborne transmission efficiency among the B.1.427, B.1.429 and ancestral B.1 (614G) variants in hamsters. These results demonstrate enhanced virulence and high relative fitness of the epsilon (B.1.427/B.1.429) variant in Syrian hamsters compared to an ancestral B.1 (614G) strain. Author SummaryIn the last 12 months new variants of SARS-CoV-2 have arisen in the UK, South Africa, Brazil, India, and California. New SARS-CoV-2 variants will continue to emerge for the foreseeable future in the human population and the potential for these new variants to produce severe disease and evade vaccines needs to be understood. In this study, we used the hamster model to determine the epsilon (B.1.427/429) SARS-CoV-2 strains that emerged in California in late 2020 cause more severe disease and infected hamsters have higher viral loads in the upper respiratory tract compared to the prior B.1 (614G) strain. These findings are consistent with human clinical data and help explain the emergence and rapid spread of this strain in early 2021.

microbiology↗

bioRxiv2019

Close relationships between coral-associated Chromera strains despite differences within the Symbiodiniaceae

Reef-building corals live in a mutualistic relationship with photosynthetic algae (family Symbiodiniaceae) that usually provide most of the energy required by the coral host. This relationship is sensitive to temperature stress; as little as a 1{degrees}C increase often leading to collapse of the association. This sensitivity has led to interest in the potential of more stress tolerant algae to supplement or substitute for the normal Symbiodiniaceae mutualists. In this respect, the apicomplexan-like microalga Chromera is of particular interest due to its greater temperature tolerance. We generated a de novo transcriptome for a Chromera strain isolated from a GBR coral ("GBR Chromera") and compared to those of the reference strain of Chromera ("Sydney Chromera"), and to those of Symbiodiniaceae (Fugacium, Cladocopium and Breviolum), as well as the apicomplexan parasite, Plasmodium falciparum. By contrast with the Symbiodiniaceae, the two Chromera strains had a high level of sequence similarity evident by very low levels of divergence in orthologous genes. Although KEGG categories provide few criteria by which true coral mutualists might be identified, they do supply a molecular rationalization for the ubiquitous association of Cladocopium strains with Indo-Pacific reef corals. The presence of HSP20 genes may underlie the higher thermal tolerance of Chromera.

genomics↗

bioRxiv2019

Transcriptomic insights into the establishment of coral-algal symbioses from the symbiont perspective

Despite the ecological significance of the mutualistic relationship between Symbiodiniaceae and reef-building corals, the molecular machinery underpinning the establishment of this relationship is not well understood. This is especially true of the symbiont side, as previous attempts to understand the interaction between coral larvae and Symbiodiniaceae have focused nearly exclusively on the host. In the current study, Acropora tenuis planula larvae were exposed to a compatible strain of Symbiodiniaceae (Cladocopium) and the transcriptomic landscape of the symbiont profiled at 3, 12, 48 and 72 h post-exposure using RNA-Seq. The transcriptomic response of Cladocopium to the symbiotic state was complex, the most obvious feature being an extensive and generalised downregulation of gene expression. Included in this \"symbiosis-derived transcriptional repression\" were a range of stress response and immune-related genes. In contrast, genes implicated in metabolism were upregulated in the symbiotic state. Consistent with previous ecological studies, this transcriptomic response of Cladocopium implied that active translocation of metabolites to the host occurred, and thus that the mutualistic relationship can be established at the larval stage. This study provides novel insights into the transcriptomic remodelling that occurs in Symbiodiniaceae, with important implications for understanding the establishment of symbiosis between corals and their dinoflagellate partners.

genomics↗