Biology subjects

Atay, E.

Publications and source records attributed to Atay, E..

4 recordsLinked to original sources

bioRxiv2026

Extensive genomic diversity in Desulfovibrio species reveals species-specific functional traits associated with disease

Desulfovibrio spp. are associated with inflammatory diseases and human health, yet limited representative genomes and isolates hinder our understanding of their role in disease. Here, we assembled a comprehensive database of 2,658 Desulfovibrio genomes across 90 diseases and 32 countries, including 24 human isolates. Genomic analyses showed extensive species diversity and revealed disease-associated functional traits, including flagellin and virulence genes (i.e. ureases). Flagellin-mediated Toll-like receptor 5 activation was species-specific and D. desulfuricans flagellin downregulated TGF-beta signalling in murine small intestinal organoids, suggesting impaired immune tolerance. Additionally, we investigated genomic capacity for hydrogen sulfide (H2S) production, a main Desulfovibrio metabolite. While health- and disease-associated Desulfovibrio spp. mainly encoded dissimilatory sulfate reduction, tetrathionate metabolism-encoding bacteria were exclusively detected in inflammatory bowel diseases, including Proteus mirabilis and Morganella morganii. Overall, our study provides a comprehensive genomic Desulfovibrio resource and identifies new links associating strain variation, functional traits and H2S-production with inflammatory diseases.

genomics↗

bioRxiv2025

Flagellin in the human gut microbiome is a diet-adjustable adjuvant for vaccination

The intestinal microbiota is thought to modulate immune responsiveness to vaccines. Human studies on this topic, however, have yielded inconsistent results1,2. We hypothesized that the microbiome would influence innate immune responses, and thus vaccine reactogenicity, more directly than vaccine immunogenicity. To test this, we established the {micro}HEAT (Microbial-Human Ecology And Temperature) study, which longitudinally profiled the fecal microbiota, oral body temperature and serum antibody responses of 171 healthy adults (18-40 years old) before and after vaccination for SARS-CoV-2. Increased temperature after vaccination ({Delta}T) was associated with habitual diet and with baseline metabolic and immune markers. The microbiomes of {Delta}T-high ({Delta}Thi) participants were characterized by high expression of flagellin and an overabundance of the flagellated bacterium Waltera. Fecal samples from {Delta}Thi participants induced more inflammation in human cells and stronger post-vaccine temperature responses in mice compared to {Delta}Tlo samples, suggesting a causal role for the microbiome. Moreover, Waltera flagellin replicated the inflammatory phenotypes in vitro and was modulable via a dietary additive. Overall, these data suggest that flagellin from the gut microbiome stimulates innate immunity and vaccine reactogenicity, and that this axis can be manipulated via diet. These findings have implications for improving human vaccine tolerance and immunogenicity.

microbiology↗

bioRxiv2022

Human brain organoid model of maternal immune activation identifies radial glia cells as selectively vulnerable

Maternal immune activation (MIA) during the critical windows of gestation is correlated with long- term neurodevelopmental deficits in the offspring, including increased risks for autism spectrum disorder (ASD) in humans. Interleukin 6 (IL-6) derived from the gestational parent is one of the major molecular mediators, by which MIA alters the developing brain. In this study, we established a human three-dimensional (3D) in vitro model of MIA by treating induced pluripotent stem cell- derived dorsal forebrain organoids with a constitutively active form of IL-6, Hyper-IL-6. We validated our model by showing that dorsal forebrain organoids express the molecular machinery necessary for responding to Hyper-IL-6 and activate STAT signaling upon Hyper-IL-6 treatment. RNA sequencing analysis revealed the upregulation of major histocompatibility complex class I (MHCI) genes, which have been implicated with ASD. Immunohistochemical analysis as well as single-cell RNA-sequencing revealed a small increase in the proportion of radial glia cells. Single-cell transcriptomic analysis revealed the highest number of differentially expressed genes in radial glia cells with downregulation of genes related to protein translation in line with data from mouse models of MIA. Additionally, we identified differentially expressed genes not found in mouse models of MIA which might drive species-specific responses to MIA. Together, we establish a human 3D model of MIA, which can be used to study the cellular and molecular mechanisms underlying the increased risk for developing disorders such as ASD.

neuroscience↗

bioRxiv2021

Nuclear Export of Drosophila PERIOD contributes to temperature compensation of the circadian clock

Circadian clocks are self-sustained molecular oscillators controlling daily changes of behavioral activity and physiology. For functional reliability and precision the frequency of these molecular oscillations must be stable at different environmental temperatures, known as temperature compensation. Despite being an intrinsic property of all circadian clocks, this phenomenon is not well understood at the molecular level. Here we use behavioral and molecular approaches to characterize a novel mutation in the period (per) clock gene of Drosophila melanogaster, which alters a predicted nuclear export sequence (NES) of the PER protein. We show that this new perI530A allele leads to progressively longer behavioral periods and clock oscillations with increasing temperature in both clock neurons and peripheral clock cells. While the mutant PERI530A protein shows normal circadian fluctuations and post-translational modifications at cool temperatures, increasing temperatures lead to both, severe amplitude dampening and hypophosphorylation of PERI530A. We further show that PERI530A displays reduced repressor activity at warmer temperatures, presumably because it cannot inactivate the transcription factor CLOCK (CLK). With increasing temperatures nuclear accumulation of PERI530A within clock neurons is increased, suggesting that PER is normally exported out of the nucleus at warm temperatures. Consequently, downregulating the nuclear export factor CRM1 also leads to temperature-dependent changes of behavioral rhythms. In summary, our results suggest that the PER NES and the nuclear export of clock proteins play an important role in temperature compensation of the Drosophila circadian clock.

neuroscience↗