Biology subjects

Francis, O.

Publications and source records attributed to Francis, O..

6 recordsLinked to original sources

bioRxiv2026

Twenty-five new microsporidian genomes: Insights into ploidy, reproduction, and the group's pangenome

Microsporidia are single-celled, obligately intracellular eukaryotic parasites of growing importance. Many aspects of their biology remain enigmatic, partly because of difficulties in sampling, culturing, and experimentally manipulating them. Here, we continue efforts to generate microsporidian genomes from serendipitously infected organisms sequenced for biodiversity genomics initiatives, such as the Darwin Tree of Life Project. We present 25 new microsporidian genomes: 14 biologically complete, including several at (near-)chromosome level, and 11 partial. Using RNA-seq data for three published genomes we identify Prokka as a suitable ab initio annotation approach for Microsporidia. Consistently annotating all available genomes, we investigate gene-content diversity across microsporidian clades. We find that the microsporidian pangenome exhibits extreme diversity, and that current genomic data substantially undersample the group's proteome space. Neither GC content nor genome span consistently explains orthogroup number across lineages, suggesting different evolutionary pressures. We find few one-to-one orthogroups in Microsporidia, as well as few orthogroups that are both lineage-specific and conserved across most species within a given lineage. Finally, Hi-C data confirm that tetraploid Amblyosporida microsporidia occur as two equivalent diploid units. In contrast, one Enterocytozoonida tetraploid genome suggests that all four genome copies occur within a single nucleus (a 'monokaryon'), confirming a previous proposal.

genomics↗

bioRxiv2026

Quantified duplications of proteins within complexes across eukaryotes

Protein complexes are central to cell biology and typically verified via a combination of interaction data, complete genome sequencing and comprehensive protein-coding gene predictions for reference eukaryotes. However this data is lacking for non-reference eukaryotes. Protein complexes can be predicted in species for which no interaction data is available by mapping orthology of verified protein complex components from reference eukaryotes to predicted proteomes. Studies that map conservation of protein complex components by orthology are often limited to a small number of protein queries, an under-representation of non-reference, microbial eukaryotes and are scattered across the literature. Here, I integrate orthology and protein interaction data by mapping proteins of experimentally verified complexes to orthogroups of proteins spanning 31 diverse eukaryotes. Proteins within complex-harbouring orthogroups are retained and distributed more evenly across taxa than non-complex orthogroups. I identified 184 universal orthogroups that included orthologs of known protein complex components from all 31 eukaryotes, consistent with a conserved core repertoire, likely present in the last eukaryotic common ancestor (LECA). I generated the protein complex orthology cartographer (PCOC) suite to find significant duplications and reductions of proteins in universal orthogroups across and between eukaryotes. This revealed both multi-copy and notably single-copy proteins, in all queried species, from the exosome, spliceosome, proteasome, small-ribosomal processome, tRNA synthetases, MCM complexes and RNA polymerase III. Case analyses of Naegleria gruberi and Guillardia theta highlight taxon-specific expansions and show how broader protist inclusion improves domain-wide inference of eukaryotic protein-complex evolution.

bioinformatics↗

bioRxiv2025

Hepatoprotective Effects of Vernonia amygdalina Leaf Extract: In Vivo and In Silico Evidence Against Ethanol-Induced Liver Injury

Alcoholic liver disease (ALD) remains a major global health burden with limited therapeutic options. In this study, we investigated the hepatoprotective effects of Vernonia amygdalina (VA) leaf extract against ethanol-induced liver injury using integrated in vivo and in silico approaches. Wistar rats were exposed to ethanol to induce liver damage, followed by treatment with VA extract (100-300 mg/kg) or silymarin (50 mg/kg). Liver function indices were evaluated through biochemical analysis. Network pharmacology analysis was performed to identify active compounds and their protein targets, and molecular docking assessed the binding affinities of key compounds. Ethanol exposure markedly increased serum SGOT, SGPT, ALKP, and total bilirubin while decreasing total protein and albumin. VA treatment significantly corrected these alterations in a dose-dependent manner. At 300 mg/kg, VA reduced SGPT from 110.31 to 88.65 U/mL, ALKP from 52.20 to 28.14 U/mL, and total bilirubin from 1.19 to 0.59 g/dL. Network pharmacology revealed flavonoids and sesquiterpene lactones as key active compounds targeting ALD-relevant proteins, including AKT1, CASP3, and HSP90AA1. Molecular docking demonstrated strong binding affinities (-9.5 kcal/mol) of cryptolepine, luteolin, and apigenin with AKT1 and HSP90AA1. VA provides both biochemical and mechanistic protection against ethanol-induced liver damage, highlighting its therapeutic potential in ALD management.

pharmacology and toxicology↗

bioRxiv2023

Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine

COVID-19 continues to damage populations, communities and economies worldwide. Vaccines have reduced COVID-19-related hospitalisations and deaths, primarily in developed countries. Persisting infection rates, and highly transmissible SARS-CoV-2 Variants of Concern (VOCs) causing repeat and breakthrough infections, underscore the ongoing need for new treatments to achieve a global solution. Based on ADDomer, a self-assembling protein nanoparticle scaffold, we created ADDoCoV, a thermostable COVID-19 candidate vaccine displaying multiple copies of a SARS-CoV-2 receptor binding motif (RBM)-derived epitope. In vitro generated neutralising nanobodies combined with molecular dynamics (MD) simulations and electron cryo-microscopy (cryo-EM) established authenticity and accessibility of the epitopes displayed. A Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Antibodies generated by immunising mice cross-reacted with VOCs including Delta and Omicron. Our study elucidates nasal administration of ADDomer-based nanoparticles for active and passive immunisation against SARS-CoV-2 and provides a blueprint for designing nanoparticle reagents to combat respiratory viral infections.

biochemistry↗

bioRxiv2020

Magnitude and kinetics of T cell and antibody responses during H1N1pdm09 infection in outbred and inbred Babraham pigs

We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize {beta}, {gamma}{delta} T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to day 4-5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from day 5-6 post infection reaching a peak at 9-14 days. {gamma}{delta} cells produced cytokines ex vivo at day 2 post infection, while virus specific IFN{gamma} producing {gamma}{delta} T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4 and {gamma}{delta} cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyse immune responses to influenza.

immunology↗

bioRxiv2020

CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor

CD8+ T cells are inherently cross-reactive and recognize numerous peptide antigens in the context of a given major histocompatibility complex class I (MHCI) molecule via the clonotypically expressed T cell receptor (TCR). The lineally expressed coreceptor CD8 interacts coordinately with MHCI at a distinct and largely invariant site to slow the TCR/peptide-MHCI (pMHCI) dissociation rate and enhance antigen sensitivity. However, this biological effect is not necessarily uniform, and theoretical models suggest that antigen sensitivity can be modulated in a differential manner by CD8. We used an intrinsically controlled system to determine how the relationship between the TCR/pMHCI interaction and the pMHCI/CD8 interaction affects the functional sensitivity of antigen recognition. Our data show that modulation of the pMHCI/CD8 interaction can reorder the agonist hierarchy of peptide ligands across a spectrum of affinities for the TCR. SIGNIFICANCESufficient immune coverage of the peptide universe within a finite host requires highly degenerate T cell receptors (TCRs). However, this inherent need for antigen cross-recognition is associated with a high risk of autoimmunity, which can only be mitigated by a process of adaptable specificity. We describe a mechanism that resolves this conundrum by allowing individual clonotypes to focus on specific peptide ligands without alterations to the structure of the TCR.

immunology↗