Biology subjects

Barry, D.

Publications and source records attributed to Barry, D..

5 recordsLinked to original sources

bioRxiv2025

3D spatial transcriptomics reveals the molecular domain structure of the mouse olfactory bulb

A core organizing principle of the vertebrate brain is its symmetry along multiple axes. However, the precision with which neurons, circuit modules, and brain regions align to these axes remains poorly understood. Here, we used 3D spatial transcriptomics to reconstruct the anatomical and molecular organization of the mouse olfactory bulb. We mapped the positions of nearly one thousand molecularly distinct glomeruli, the structural and functional units of odor processing, revealing highly symmetric organization across hemispheres. Within each bulb, we delineated a curved axis of symmetry that divides pairs of sister glomeruli. Gene expression in the olfactory epithelium predicted glomerular position with near-glomerular resolution. However, glomerular symmetry did not extend to deeper layer mitral and granule cells, suggesting a reorganization from sensory input to cortical output pathways. Our findings provide the first comprehensive map of the olfactory bulb and reveal how its molecular structure is instructed by epithelial gene expression programs.

neuroscience↗

bioRxiv2024

Zebrafish reveal new roles for Fam83f in hatching and the DNA damage-mediated autophagic response

The FAM83 (Family with sequence similarity 83) family is highly conserved in vertebrates, but little is known of the functions of these proteins beyond their association with oncogenesis. Of the family, FAM83F is of particular interest because it is the only membrane-targeted FAM83 protein. When over-expressed, FAM83F activates the canonical Wnt signalling pathway and binds to and stabilizes p53; it therefore interacts with two pathways often dysregulated in disease. Insights into gene function can often be gained by studying the roles they play during development, and here we report the generation of fam83f knock-out (KO) zebrafish, which we have used to study the role of Fam83f in vivo. We show that endogenous fam83f is most strongly expressed in the hatching gland of developing zebrafish embryos, and that fam83f KO embryos hatch earlier than their wild-type (WT) counterparts, despite developing at a comparable rate. We also demonstrate that fam83f KO embryos are more sensitive to ionizing radiation than WT embryos--an unexpected finding, bearing in mind the previously-reported ability of FAM83F to stabilize p53. Transcriptomic analysis shows that loss of fam83f leads to downregulation of phosphatidylinositol-3-phosphate (PI(3)P) binding proteins and impairment of cellular degradation pathways, particularly autophagy, a crucial component of the DNA damage response. Finally, we show that Fam83f protein is itself targeted to the lysosome when over-expressed in HEK293T cells, and that this localization is dependent upon a C terminal signal sequence. The zebrafish lines we have generated suggest that Fam83f plays an important role in autophagic/lysosomal processes, resulting in dysregulated hatching and increased sensitivity to genotoxic stress in vivo.

developmental biology↗

bioRxiv2023

MiR-155 epigenetically counteracts hypoxia for mitochondrial fitness during germinal center positive selection

To increase antibody affinity against pathogens, positively selected GC-B cells initiate cell division in the light zone (LZ) of germinal centres (GCs). Among those, higher-affinity clones migrate to the dark zone (DZ) and vigorously proliferate by relying on oxidative phosphorylation (OXPHOS). However, it remains unknown how positively selected GC-B cells adapt their metabolism for cell division in the glycolysis-dominant, cell cycle arrest-inducing, hypoxic LZ microenvironment. Here, we show that microRNA (miR)-155 mediates metabolic reprogramming during positive selection to protect high-affinity clones. Transcriptome examination and mass spectrometry analysis revealed that miR-155 regulates H3K36me2 levels by directly repressing hypoxia-induced histone lysine demethylase, Kdm2a. This is indispensable for enhancing OXPHOS through optimizing the expression of vital nuclear mitochondrial genes under hypoxia. The miR-155-Kdm2a interaction is crucial to prevent excessive production of reactive oxygen species and apoptosis. Thus, miR-155-mediated epigenetic regulation promotes mitochondrial fitness in high-affinity clones, ensuring their expansion and consequently affinity maturation.

immunology↗

bioRxiv2022

Comparative Mucomic Analysis of Three Functionally Distinct Cornu aspersum Secretions

Every animal secretes mucus, placing them among the most diverse biological materials. Mucus hydrogels are complex mixtures of water, ions, carbohydrates, and proteins. Uncertainty surrounding their composition and how interactions between components contribute to mucus function complicates efforts to exploit their properties. There is substantial interest in commercializing mucus from the garden snail, Cornu aspersum, for skincare, drug delivery, tissue engineering, and composite materials. C. asperum secretes three mucus -- one shielding the animal from environmental threats, one adhesive mucus from the pedal surface of the foot, and another pedal mucus that is lubricating. It remains a mystery how compositional differences account for their substantially different properties. Here, we characterize mucus proteins, glycosylation, ion content, and mechanical properties to understand structure-function relationships through an integrative "mucomics" approach. We identify new macromolecular components of these hydrogels, including a novel protein class termed Conserved Anterior Mollusk Proteins (CAMPs). Revealing differences between C. aspersum mucus shows how considering structure at all levels can inform the design of mucus-inspired materials.

biochemistry↗

bioRxiv2020

Hospital outbreak of carbapenem-resistant Enterobacteriales associated with an OXA-48 plasmid carried mostly by Escherichia coli ST399

A hospital outbreak of carbapenem-resistant Enterobacteriales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacteriales were involved in the outbreak. Escherichia coli ST399 accounted for 20/55 of all the isolates. Comparative genomics with publicly available E. coli ST399 sequence data showed that the outbreak isolates formed a unique clade. The OXA-48 plasmid identified in the outbreak differed from other known plasmids by an estimated five homologous recombination events. We estimated a lower bound to the plasmid conjugation rate to be 0.23 conjugation events per lineage per year. Our analysis suggests co-evolution between the plasmid and its main bacterial host to be a key driver of the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying OXA48 as the main cause of a plasmid-borne outbreak within a hospital setting. This study supports complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.

evolutionary biology↗