Biology subjects

Vernon, S.

Publications and source records attributed to Vernon, S..

5 recordsLinked to original sources

bioRxiv2026

The phosphatidylserine-binding proteins Turandots protect the peripheral nervous system from antimicrobial peptide toxicity

Inflammation increases with aging and contributes to neurodegeneration, yet the principles that determine how immune effectors target host neural tissue remain poorly understood. Antimicrobial peptides (AMPs) are central components of innate immune defenses strongly induced upon infection and upon aging. Studies have shown that AMPs can exhibit cytotoxicity toward host cells, pointing to a role in neurodegeneration. We show that cationic AMPs selectively bind and damage motoneurons that expose phosphatidylserine (PS), an anionic phospholipid normally restricted to the inner leaflet of the plasma membrane. Both infection and aging increase neuronal PS exposure alongside AMP expression. AMP binding occurs in a PS-dependent manner, leading to synaptic bouton fragmentation, accelerated neuronal aging, and locomotor decline. This toxicity is prevented in Drosophila by Turandot proteins, which reduce AMP-PS interactions on motoneurons. Together, our findings define a molecular mechanism underlying neuronal susceptibility to immunopathology and a set of proteins with neuroprotective potential. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=179 HEIGHT=200 SRC="FIGDIR/small/721952v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@ca817aorg.highwire.dtl.DTLVardef@fa8cb0org.highwire.dtl.DTLVardef@12a8bd4org.highwire.dtl.DTLVardef@423907_HPS_FORMAT_FIGEXP M_FIG This study shows that infection or dysbiosis in Drosophila can simultaneously induce antimicrobial peptide expression while promoting phosphatidylserine (PS) exposure on neurons at the neuromuscular junction. Cationic antimicrobial peptides contribute to neurodegeneration by binding to neurons that expose negatively charged phospholipids such as PS. In Drosophila, a family of secreted peptides, the Turandot proteins, can protect the peripheral nervous system by binding to PS-exposed membranes. Together, these findings reveal a role for antimicrobial peptides, a key component of innate immunity, in promoting neurodegeneration as well as a potential protective mechanism by PS masking agent. C_FIG

immunology↗

bioRxiv2025

Characterization of nitrogenase genes nifP and nifVZT1 in the cyanobacterium Anabaena (Trichormus) variabilis ATCC 29413

Anabaena (Trichormus) variabilis ATCC 29413 is a heterocyst-forming cyanobacterium with two Mo-nitrogenases encoded by the large nif1 and nif2 gene clusters. The nif1-encoded nitrogenase is expressed in heterocysts under oxic growth conditions, whereas the nif2-encoded nitrogenase is expressed only in anoxic vegetative cells. The nifP and nifVZT1 genes are contiguous and distinct from the major nif1 and nif2 clusters, suggesting that nifP and nifVZT1 may be cotranscribed. However, we identified primary transcription start sites for nifP and nifVZT1, indicating that each has its own promoter. The promoter region of nifP shares multiple conserved motifs with the nifB1 and nifB2 promoters, which are regulated by homologous transcriptional activators CnfR1 and CnfR2, respectively. These conserved motifs are not present in the promoter region of nifVZT1. Using nifP promoter fragments that included or excluded the conserved motifs fused to reporter gene lacZ, we determined which motifs contributed to nifP expression; however, these identified motifs differed from the conserved motifs shown previously to regulate nifB1 or nifB2 transcription. Further, the regulation of transcription requires a region inside the coding region of nifP. Mutant strains lacking nifP or nifVZT1 grew well in the absence of fixed nitrogen and showed no reduction in nitrogenase activity compared to the wild-type strain grown under oxic or anoxic conditions. Further, nifP was expressed constitutively in vegetative cells grown -N or +N, but its expression increased greatly in heterocysts by CnfR1 activation of the nifP promoter. In contrast, nifVZT1 was expressed only in heterocysts but, unlike most other nif1 genes, was not under the control of CnfR1.

microbiology↗

bioRxiv2023

Construction and optimization of multi-platform precision pathways for precision medicine

In the enduring challenge against disease, advancements in medical technology have empowered clinicians with novel diagnostic platforms. Whilst in some cases, a single test may provide a confident diagnosis, often additional tests are required. However, to strike a balance between diagnostic accuracy and cost-effectiveness, one must rigorously construct the clinical pathways. Here, we developed a framework to build multi-platform precision pathways in an automated, unbiased way, recommending the key steps a clinician would take to reach a diagnosis. We achieve this by developing a confidence score, used to simulate a clinical scenario, where at each stage, either a confident diagnosis is made, or another test is performed. Our framework provides a range of tools to interpret, visualize and compare the pathways, improving communication and enabling their evaluation on accuracy and cost, specific to different contexts. This framework will guide the development of novel diagnostic pathways for different diseases, accelerating the implementation of precision medicine into clinical practice.

bioinformatics↗

bioRxiv2021

Multi-omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system, debilitating disability manifesting as severe fatigue and post-exertional malaise. The chronic dysfunctions in ME/CFS are increasingly recognized as significant health factors with potential parallels with long COVID. However, the etiology of ME/CFS remains elusive with limited high-resolution human studies. In addition, reliable biomarker-based diagnostics have not been well-established, but may assist in disease classification, particularly during different temporal phases of the disease. Here, we performed deep multi- omics (shotgun metagenomics of gut microbiota and plasma metabolomics) and clinical phenotyping of healthy controls (n=79) vs. two cohorts of ME/CFS patients - those with short-term disease (<4 years, n=75), and patients with long-term disease (>10y, n=79). Overall, ME/CFS was characterized by reduced gut microbiome diversity and richness with high heterogeneity, and depletion of sphingomyelins and short-chain fatty acids in the plasma. We found significant differences when stratifying by cohort; short-term ME/CFS was associated with more microbial dysbiosis, but long-term ME/CFS was associated with markedly more severe phenotypic and metabolic abnormalities. We identified a reduction in the gene-coding capacity (and relative abundance of butyrate producers) of microbial butyrate biosynthesis together with a reduction in the plasma concentration of butyrate, especially in the short-term group. Global co-association and detailed gene pathway correlation analyses linking the microbiome and metabolome identified additional potential biological mechanisms underlying host-microbiome interactions in ME/CFS, including bile acids and benzoate pathways. Finally, we built multiple state-of-the-art classifiers to identify microbes, microbial gene pathways, metabolites, and clinical features that individually or together, were most able to differentiate short or long-term MECFS, or MECFS vs. healthy controls. Taken together, our study presents the highest resolution, multi-cohort and multi- omics analysis to date, providing an important resource to facilitate mechanistic hypotheses of host-microbiome interactions in ME/CFS.

microbiology↗

bioRxiv2017

Genome-Epigenome Interactions Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an example of a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as with specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, the association between DNA methylation and genetic background in relation to the ME/CFS is currently unknown. In this study we explored this association by characterizing the genomic (~4.3 million SNPs) and epigenomic (~480 thousand CpG loci) variability between populations of ME/CFS patients and healthy controls. We found significant associations of methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation phenotypes associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.

genomics↗