Biology subjects

McGarry, A.

Publications and source records attributed to McGarry, A..

4 recordsLinked to original sources

bioRxiv2024

The holobiont's extracellular microbiome modulates the adaptation of an intracellular endosymbiont

Holobionts contain spatially separated microbes whose interorgan effects are a neglected source of potential, functional variation. Here we show the extracellular gut microbiome modulates the transcriptome and adaptation of the endosymbiont Wolbachia in Drosophila melanogaster testes. Gut bacteria suppress cytoplasmic incompatibility (CI), a sperm-egg lethality trait, by altering endosymbiont pathogenicity gene expression. Transgenic assays identify the enchancer of cytoplasmic incompatibility gene eci as causal to the variation. Restoring the gut microbiome in laboratory and wild-caught, germ-free flies recapitulates CI attenuation and shifts host fitness. Intact holobionts sustain higher densities of the two symbiont types versus isolated rearing, revealing a synergistic, replication interaction between the symbiont classes. The gut-germline axis on symbiont functions has far-reaching implications for the study of holobiont trait variation.

microbiology↗

bioRxiv2023

Synthetic autotetraploid Caenorhabditis elegans resist severe cold stress by escaping cold induced death at the gravid adult stage.

Whole genome duplication (WGD) is a well-studied yet enigmatic phenomenon. While it has long been recognised as contributing numerous genes to many eukaryotic lineages and often implicated in evolutionary radiations, how these lineages overcome the known burdens of polyploidy is poorly understood. Circumstantial evidence of many WGD events coinciding with periods of otherwise mass extinction is consistent with the hypothesis that polyploidy is conditionally advantageous under stress conditions. While support for this comes from both theoretical work and field studies, direct evidence is lacking, especially in animals. Here we compare diploid and neo-tetraploid Caenorhabditis elegans and show that tetraploid animals exhibit increased resilience under specific stress conditions related to temperature changes. Most notably, under severe cold stress gravid neo-tetraploids massively escape cold-induced death, and generate more progeny, of similar quality, than diploid animals. This is the first demonstration of the effects of polyploidy on stress resistance and physiology in animals.

cell biology↗

bioRxiv2021

Single nuclear transcriptional signatures of dysfunctional brain vascular homeostasis in Alzheimer's disease

Brain perfusion and normal blood brain barrier integrity are reduced early in Alzheimers disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and control brains to characterise pathological transcriptional signatures. We found that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. EC transcriptional signatures identified mechanisms for impaired {beta}-amyloid clearance. Evidence for immune activation was found with upregulation of interferon signalling genes in EC and in pericytes (PC). Transcriptional signatures suggested dysregulation of vascular homeostasis and angiogenesis with upregulation of pro-angiogenic signals (HIF1A) and metabolism in EC, but downregulation of homeostatic growth factor pathways (VEGF, EGF, insulin) in EC and PC and of extracellular matrix genes in fibroblasts (FB). Our genomic dissection of vascular cell risk gene enrichment suggests a potentially causal role for EC and defines transcriptional signatures associated with microvascular dysfunction in AD.

neuroscience↗

bioRxiv2021

Diverse human astrocyte and microglial transcriptional responses to Alzheimer's pathology

To better define roles that astrocytes and microglia play in Alzheimers disease (AD), we used single-nuclei RNA sequencing to comprehensively characterize transcriptomes in astrocyte and microglia nuclei isolated post mortem from neuropathologically-defined AD and control brains with a range of amyloid-beta and phospho-tau (pTau) pathology. Significant differences in glial gene expression (including AD risk genes expressed in astrocytes [CLU, MEF2C, IQCK] and microglia [APOE, MS4A6A, PILRA]) were correlated with tissue amyloid and pTau expression. Astrocytes were enriched for proteostatic, inflammatory and metal ion homeostasis pathways. Pathways for phagocytosis, proteostasis and autophagy were highly enriched in microglia and perivascular macrophages. Gene co-expression analyses revealed potential functional associations of soluble biomarkers of AD in astrocytes (CLU) and microglia (GPNMB). Our work highlights responses of both astrocytes and microglia for pathological protein clearance and inflammation, as well as glial transcriptional diversity in AD.

neuroscience↗