Biology subjects

Murray, V.

Publications and source records attributed to Murray, V..

6 recordsLinked to original sources

bioRxiv2026

Alterations to the yeast chromatin landscape during hypoxia

When cells encounter low oxygen conditions, signaling events target key transcription factors to reprogram gene expression to promote cell survival and adaptation under this challenging environmental stress. The substantial metabolic changes that occur in hypoxia also drive changes to the chromatin environment due to altered cofactor availability and direct oxygen sensitivity of chromatin-modifying enzymes, among other factors. Given the links between hypoxic cellular environments and numerous pathophysiological processes, including tumor progression and metastasis, cardiovascular disorders, and aberrant development, it is critical to understand the chromatin states and chromatin-based regulatory mechanisms associated with cellular responses to hypoxia. Here, we used the model eukaryote Saccharomyces cerevisiae to interrogate the requirement for key transcription factors and chromatin regulators in survival during hypoxia and we assessed the distribution of major histone modifications associated with the response to stress, H3K9 acetylation and H3K4 methylation, throughout the genome during hypoxia. Our results show that only a small number of chromatin modifiers in yeast contribute to survival in hypoxia; however, there are substantial changes to the abundance and distribution of both H3K9ac and H3K4me3 during hypoxic growth. Specifically, H3K9ac levels are reduced throughout the genome though still maintain association with transcriptionally active genes. H3K4me3 has increased abundance genome-wide and shows a wider distribution with greater abundance in coding sequences particularly of genes upregulated in hypoxic conditions. Altogether, our data demonstrate substantial changes to the chromatin landscape in hypoxic conditions in the budding yeast model, providing key insights into physiological chromatin changes caused by limiting oxygen in the environment.

molecular biology↗

bioRxiv2026

BehaviorScope-X: reusing pose-trained visual representations for full-video ethology

Pose-estimation pipelines usually export keypoint coordinates and discard the intermediate visual representations learned to localize animals in a specific assay. We asked whether those discarded representations can be reused for full-video ethology. BehaviorScope-X tests this idea by treating a trained pose checkpoint as both a keypoint estimator and a reusable visual encoder: the pose model is run once to cache detections, keypoints, pose-derived social geometry, and frozen intermediate descriptors, after which compact temporal classifiers are trained on cached multimodal windows. Across MARS resident-intruder videos, cached pose-trained descriptors and pose-derived geometry provided complementary evidence for behavior decoding, recovering sustained behavioral episodes and local sequence structure while revealing a main limitation in dense short-bout regions. The same cache-and-classify design generalized across pose routes, including a MobileNetV3 backbone and a DeepLabCut SuperAnimal HRNet-W32 checkpoint, showing that standard pose workflows can expose behavior-relevant visual descriptors without giving up their keypoint-estimation role. We further tested the approach in Fly-v-Fly aggression, extending the analysis to a second species and shorter behavioral time scale, where sub-second events and annotation-boundary uncertainty limited strict bout recovery. End-to-end profiling showed that the workflow can operate near-real-time or real-time on consumer hardware. Together, these experiments support amortized pose vision as a practical strategy for reusing assay-trained pose models as stable sources of visual and geometric evidence for scalable behavioral analysis. Author summaryPose-estimation models are usually used to convert animal video into body landmarks, while the same models internal visual representations are discarded. We ask whether the model that estimates pose can also provide visual features for behavior analysis. Our workflow runs a trained pose model once, caches its landmarks, pose-derived interaction geometry, and internal visual features, and trains compact behavior classifiers on that cache. Across multiple pose backbones and pose-estimation workflows, these shared pose-and-visual signals supported full-video ethogram recovery without training a separate video network. This turns pose training into a reusable source of assay-specific visual and geometric evidence for scalable behavioral analysis. HighlightsO_LIA pose-estimation checkpoint is reused as both keypoint estimator and visual encoder. C_LIO_LIA single pose-inference pass caches keypoints, social geometry, and intermediate visual descriptors. C_LIO_LICached pose-derived visual and geometric evidence improves full-video behavior decoding beyond pose-derived features alone. C_LIO_LIBehaviorScope-X turns existing pose workflows into reusable full-video behavior-analysis pipelines. C_LI

neuroscience↗

bioRxiv2025

A new resource of clonal pluripotent human stem cell lines exhibiting inter- and intra-embryo consistency and variability

Human naive pluripotent stem cells can generate all somatic tissues and extra-embryonic components of the blastocyst. We derived multiple clonal naive pluripotent stem cell lines from individual embryos by physical separation of inner cell mass cells and subsequent individual expansion of each resulting dome-shaped colony, providing the foundation for a resource to investigate intra- and inter-embryo variation. Twenty lines were derived from ten embryos donated from nine couples. While differences between lines are observed, the overarching pluripotency circuitry is preserved in each. They can differentiate into extra-embryonic lineages and readily acquire post-implantation pluripotent identity when exposed to culture conditions driving in vitro capacitation, subsequently to generate derivatives of the three germ layers: ectoderm, mesoderm and endoderm. Some lines exhibit intra-chromosomal amplification and deletions and are therefore anticipated to provide a valuable, accessible system for modelling chromosomal mosaicism and its potential consequences using chimeric organoids, such as blastoids and gastruloids.

developmental biology↗

bioRxiv2022

Mild SARS-CoV-2 infection results in long-lasting microbiota instability

Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of SARS-CoV-2 infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting. To address this knowledge gap, we longitudinally sampled 14 SARS-CoV-2 positive subjects who remained outpatient and 4 household controls. SARS-CoV-2 cases exhibited a significantly less stable gut microbiota relative to controls, as long as 154 days after their positive test. These results were confirmed and extended in the K18-hACE2 mouse model, which is susceptible to SARS-CoV-2 infection. All of the tested SARS-CoV-2 variants significantly disrupted the mouse gut microbiota, including USA-WA1/2020 (the original variant detected in the United States), Delta, and Omicron. Surprisingly, despite the fact that the Omicron variant caused the least severe symptoms in mice, it destabilized the gut microbiota and led to a significant depletion in Akkermansia muciniphila. Furthermore, exposure of wild-type C57BL/6J mice to SARS-CoV-2 disrupted the gut microbiota in the absence of severe lung pathology. IMPORTANCETaken together, our results demonstrate that even mild cases of SARS-CoV-2 can disrupt gut microbial ecology. Our findings in non-hospitalized individuals are consistent with studies of hospitalized patients, in that reproducible shifts in gut microbial taxonomic abundance in response to SARS-CoV-2 have been difficult to identify. Instead, we report a long-lasting instability in the gut microbiota. Surprisingly, our mouse experiments revealed an impact of the Omicron variant, despite producing the least severe symptoms in genetically susceptible mice, suggesting that despite the continued evolution of SARS-CoV-2 it has retained its ability to perturb the intestinal mucosa. These results will hopefully renew efforts to study the mechanisms through which Omicron and future SARS-CoV-2 variants alter gastrointestinal physiology, while also considering the potentially broad consequences of SARS-CoV-2-induced microbiota instability for host health and disease.

microbiology↗

bioRxiv2021

mRNA vaccine-induced SARS-CoV-2-specific T cells recognize B.1.1.7 and B.1.351 variants but differ in longevity and homing properties depending on prior infection status

While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naive and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naive individuals, the second dose boosted the quantity and altered the phenotypic properties of SARS-CoV-2-specific T cells, while in convalescents the second dose changed neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naive vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx. These results provide reassurance that vaccine-elicited T cells respond robustly to emerging viral variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2-specific T cells compared to their infection-naive counterparts.

immunology↗

bioRxiv2021

Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence

CD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but a detailed characterization of these cells has been hampered by technical challenges. We screened 21 well-characterized, longitudinally-sampled convalescent donors that recovered from mild COVID-19 against a collection of SARS-CoV-2 tetramers, and identified one participant with an immunodominant response against Nuc322-331, a peptide that is conserved in all the SARS-CoV-2 variants-of-concern reported to date. We conducted 38- parameter CyTOF phenotyping on tetramer-identified Nuc322-331-specific CD8+ T cells, and on CD4+ and CD8+ T cells recognizing the entire nucleocapsid and spike proteins from SARS- CoV-2, and took 32 serological measurements on longitudinal specimens from this participant. We discovered a coordination of the Nuc322-331-specific CD8+ T response with both the CD4+ T cell and antibody pillars of adaptive immunity. Nuc322-331-specific CD8+ T cells were predominantly central memory T cells, but continually evolved over a [~]6-month period of convalescence. We observed a slow and progressive decrease in the activation state and polyfunctionality of the Nuc322-331-specific CD8+ T cells, accompanied by an increase in their lymph-node homing and homeostatic proliferation potential. These results suggest that following a typical case of mild COVID-19, SARS-CoV-2-specific CD8+ T cells not only persist but continuously differentiate in a coordinated fashion well into convalescence, into a state characteristic of long-lived, self-renewing memory.

immunology↗