Biology subjects

Field, S.

Publications and source records attributed to Field, S..

8 recordsLinked to original sources

bioRxiv2026

Novel Methylation Markers in a Prostate Cancer Cohort are Associated with Disease Development and Relapse

Prostate cancer remains one of the most common cancers among men globally. While significant strides have been made in diagnosis and treatment, understanding the complex genetic and epigenetic underpinnings of the disease remains crucial for guiding intervention and developing more personalized and effective therapies. The importance of DNA methylation in prostate cancer has been known for some time, but important facets of the modulation of the epigenome during carcinogenesis remain obscure, partly because the bulk of cancer methylation data have been produced using microarray technologies. Here we utilise the TruSeq methyl capture method (EPICseq) to profile the, previously defined, UK Prostate ICGC cohort of well-annotated primary prostate cancers. To this we add methylation sequencing of benign tissue from the same men. These data allow us to identify differentially methylated regions distinguishing cancerous and non-cancerous prostate tissue, while identifying numerous genes whose methylation profiles can perform that task as well as distinguishing between classes of prostate cancer. We describe a describe a methylation-based control mechanism for prostate-cancer-associated SNPs, and show that this seems a likely mechanism of action for a SNP near the MMP7 gene. We describe three novel molecular signatures that arise from different aspects of the biology of prostate cancer revealed by sequencing. Each is shown to be an independent classifier of cancers into groups with different expected times to relapse. These consist of patterns in driver gene methylation, strand-specific methylation, and signal arising in mitochondrial reads. We show that these signatures, combined with existing molecular tools, provide a powerful predictor of time to recurrence. By substantially enhancing understanding of prostate cancer risk, detection, and prognosis, we pave the way for the development of clinical practices that will benefit patients and improve outcomes.

cancer biology↗

bioRxiv2025

Comparative genomics reveals multipartite genomes undergoing loss in the fungal endosymbiotic genus Mycetohabitans

Endosymbiotic bacteria extensively impact phenotypes of their eukaryotic hosts, while experiencing dramatic changes to their own genome as they become more host-restricted in lifestyle. Understanding the trajectory of such a genome has largely been done through study of animal-associated bacteria, especially insect endosymbionts. Yet, endofungal bacteria provide another natural experimental model for investigating how microbial genomes change when living inside of a host cell. Mycetohabitans spp. are culturable bacterial endosymbionts of the Mucoromycota fungus Rhizopus microsporus. To investigate the genome dynamics resulting from the endohyphal nature of this emerging model genus, we long-read sequenced and assembled new complete genomes to combine with previous assemblies, creating a global dataset of 28 complete Mycetohabitans genomes. All genomes were between 3.3 and 3.9 Mbp in size and were multipartite, structured into two conserved replicons with some strains having an additional plasmid. Based on evolutionary rate and gene content analysis of the different replicons, we termed the two major ones a chromosome and chromid. The differential presence of a third, mobilome-rich plasmid in some strains and the proliferation of transposable elements provide putative mechanisms for recombination or gene loss. The conservation of intact prophage and putative toxin-antitoxin systems, and extensive enrichment of secondary metabolite clusters in the Mycetohabitans genomes highlight the dynamic nature of this reducing genome. With fungal-bacterial symbioses becoming increasingly apparent phenomena, lessons learned from this symbiosis will inform our understanding of bacterial adaptation to novel hosts, and the process of microbe-microbe coevolution. SIGNIFICANCEGenomes change when organisms become closely associated, as bacterial partners undergo less opportunities for genetic exchange and become more reliant on their hosts. Our pangenome analysis of the endofungal genus Mycetohabitans shows a snapshot of evolution where the bacteria are moving from a facultative towards an obligate relationship with their host fungi. We find that Mycetohabitans genomes are marked by transposable elements, pseudogenes, a large biosynthetic repertoire, and novel bacteriophage. We provide a genomic resource to match publicly accessible strains for future work on endosymbiotic genetics and evolution.

genomics↗

bioRxiv2025

FLOE1 maintains cellular viscosity in rehydrating Arabidopsis embryos

Most plant embryos can survive for years in a dry state of less than 10% water(1). Rehydration during seed germination is critical but risky-too little environmental water can dehydrate and kill the developing embryo. Plants avoid this by germinating only when sufficient water is present. However, the mechanisms by which sufficient water is sensed and how it triggers germination remain unknown. FLOE1 suppresses seed germination under water limitation by undergoing reversible phase changes in response to water potential(2). To understand how FLOE1 affects germination, we compared water behavior in wild type and floe1-1 null mutants. While both had similar amounts of water when dry, floe1-1 seeds hydrated less than the wild type after imbibition. Additionally, bound water was less restricted in floe1-1 embryos, suggesting FLOE1 promotes macromolecular water binding. By developing plant-compatible versions of Genetically Encoded Multimeric nanoparticles (GEMs)(3), we show that FLOE1 increases cytoplasmic viscosity during embryo rehydration. FLOE1 in yeast was sufficient to increase cytoplasmic viscosity. FLOE1 also increased cytoplasmic viscosity during hyperosmotic stress in yeast, and this ability was ablated by FLOE1 domain deletions. Our study identifies FLOE1 as a regulator of water content, dynamics, and cytoplasmic viscosity, linking molecular water control to cellular physical properties.

plant biology↗

bioRxiv2024

Genetic and microbial analysis of invasiveness for Escherichia coli strains associated with inflammatory bowel disease

Background & AimsThe adherent-invasive Escherichia coli (AIEC) pathotype is implicated in inflammatory bowel disease (IBD) pathogenesis. AIEC strains are currently defined by phenotypic measurement of their pathogenicity, including invasion of epithelial cells. This broad definition, combined with the genetic diversity of AIEC across IBD patients, has complicated the identification of virulence determinants. We sought to quantify the invasion phenotype of clinical isolates from IBD patients and identify the genetic basis for their invasion into epithelial cells. MethodsA pangenome with core and accessory genes (genotype) was assembled using whole genome sequencing of 168 E. coli samples isolated from 13 IBD patients. A modified assay for invasion of epithelial cells (phenotype) was established with consideration of antibiotic resistance phenotypes. Isolate genotype was correlated to invasiveness phenotype to identify genetic factors that co-segregate with invasion. ResultsPangenome-wide comparisons of E. coli clinical isolates identified accessory genes that can co-segregate with invasion phenotype. These correlations found the acquisition of antibiotic resistance genes in clinical isolates compromised the traditional gentamicin protection assays used to quantify invasion. Therefore, an alternate assay, based on amikacin resistance, identified genes co-segregating with invasion. These genes encode an arylsulfatase, a glycoside hydrolase, and genetic islands carrying propanediol utilization and sulfoquinovose metabolism pathways. ConclusionsThis study highlights the importance of incorporating antibiotic resistance screening for invasion assays used in AIEC identification. Accurately screened invasion phenotypes identified accessory genome elements among E. coli IBD isolates that correlate with their ability to invade epithelial cells. These results help explain why single genetic markers for the AIEC phylotype are challenging to identify. SynopsisWe established a pangenome of Escherichia coli isolates from inflammatory bowel disease patients using whole genome sequencing. The genotypes were correlated with a newly developed measurement of invasion phenotype to identify co-segregating genes.

microbiology↗

bioRxiv2024

Arabidopsis thaliana RHAMNOSE 1 condensate formation drives UDP-rhamnose synthesis

Rhamnose is an essential component of the plant cell wall and is synthesized from uridine diphosphate (UDP)-glucose by the RHAMNOSE1 (RHM1) enzyme. RHM1 localizes to biomolecular condensates in plants, but their identity, formation, and function remain elusive. Combining live imaging, genetics, and biochemical approaches in Arabidopsis and heterologous systems, we show that RHM1 alone is sufficient to form enzymatically active condensates, which we name rhamnosomes. Rhamnosome formation is required for UDP-rhamnose synthesis and organ development. Overall, our study demonstrates a novel role for biomolecular condensation in metabolism and organismal development, and provides further support for how organisms have harnessed this biophysical process to regulate small molecule metabolism. One-Sentence SummaryCondensation of RHM1 drives UDP-rhamnose synthesis during plant development.

plant biology↗

bioRxiv2023

Photosynthetic acclimation mediates exponential growth of a desert plant in Death Valley summer

Heat waves, now more frequent and longer due to climate change, devastate plant productivity. Although rare, thermophilic plants could hold keys to engineering heat resilience in crop plants. Tidestromia oblongifolia is a thermophilic flowering plant that thrives at temperatures above 45{degrees}C. When exposed to Death Valley summer conditions, T. oblongifolia increased its thermal optimum of photosynthesis within a day and accelerated growth within 10 days. The physiological changes were accompanied by morphological, anatomical, and gene expression changes revealed by a newly sequenced genome. In bundle sheath cells where Rubisco fixes CO2, mitochondria relocated to chloroplasts and novel, cup-shaped chloroplasts appeared. Understanding how this plant acclimates under heat may afford new ways of engineering heat tolerance in crop plants. One-Sentence SummaryTidestromia oblongifolias acclimation to Death Valley is accompanied by changes in gene expression, organellar dynamics, and photosynthesis.

plant biology↗

bioRxiv2023

Microbiota epigenetically direct tuft cell differentiation to control type 2 immunity

Allergy and anti-helminth immunity are driven by type 2 responses in mucosal tissues. Tuft cells are key regulators of type 2 immunity, however the factors that control these cells remain poorly understood. Here we find that butyrate-producing commensal bacteria decrease tuft cells in the intestine. Butyrate suppression of tuft cells required the epigenetic modifying enzyme histone deacetylase 3 (HDAC3), suggesting that HDAC3 may promote tuft cell-dependent immunity. Consistent with this, epithelial-intrinsic HDAC3 actively regulated tuft cell expansion in vivo and was required to induce type 2 immune responses during helminth infection. Interestingly, butyrate epigenetically restricted stem cell differentiation into tuft cells, and inhibition of HDAC3 in adult mice and human intestinal organoids was sufficient to block tuft cell expansion. Collectively, these data reveal an epigenetic pathway in stem cells that directs tuft cell differentiation, and highlight a new level of regulation through which commensal bacteria calibrate intestinal immunity.

immunology↗

bioRxiv2021

The Arabidopsis Calcium Sensor Calmodulin-like 38 Regulates Stress Granule Autophagy and Dynamics during Low Oxygen Stress and Re-aeration Recovery

In response to the energy crisis resulting from submergence stress and hypoxia, Arabidopsis limits non-essential mRNAs translation, and accumulate cytosolic stress granules (SG). SGs are phase-separated mRNA-protein particles that partition transcripts for various fates: storage, degradation, or return to translation after stress alleviation. Here, it is shown that RNA stress granules are dynamically regulated during hypoxia stress and aerobic recovery via two phases of autophagy that require the AAA+ ATPase CDC48 and the calcium sensor Calmodulin-like 38 (CML38). CML38 is a core hypoxia response-protein that associates with hypoxia-induced SGs. We show that CML38 is essential for SG autophagy during extended hypoxia. Further, cml38 mutants show disorganized SG morphology during extended hypoxia, suggesting a role in SG formation and maintenance. We also show that upon the return of aerobic conditions, intracellular calcium and CML38 are necessary for SG breakdown and turnover, and for upregulating autophagy. cml38 mutants not only lose these responses, but also have aberrant, sustained autophagosome accumulation during the reoxygenation recovery phase. The findings suggest that CDC48 RNA granule autophagy ("granulophagy") is conserved in plants, and that the hypoxia-induced calcium sensor CML38 regulates SG autophagy during anaerobic stress as well as during the reprogramming phase associated with reoxygenation.

plant biology↗