Biology subjects

Coates, M.

Publications and source records attributed to Coates, M..

8 recordsLinked to original sources

bioRxiv2026

Emergent particle collection by cyanobacteria through gliding motility and filament buckling

Cyanobacterial macrostructures such as mats, aggregates, and stromatolites are observed in diverse habitats. These structures incorporate organic and inorganic matter and form microenvironments enabling biochemical transformations. Macrostructures are found to be associated with motile, filamentous cyanobacteria, but to what extent, and how filament motility can drive macrostructure formation is unclear. To address this question, we study macrostructure formation in a well-characterised freshwater cyanobacterial community dominated by the filamentous cyanobacterium Fluctiforma draycotensis. We discover an emergent particle collection behaviour that results in aggregate macrostructures composed of a solid core surrounded by an outer layer dominated by entangled cyanobacterial filaments. We show that the particle collection and subsequent aggregate formation result from the gliding motility of the cyanobacteria. Developing a novel 3D model of active filament movement, we analyse how filament morphology and mechanical properties affect movement dynamics, particle collection, and filament entanglement. We predict that particle collection requires filaments above a certain length and flexibility. We confirm the resulting prediction of length dependence of particle collection behavior with shortened filaments of F. draycotensis and naturally short Pseudanabaena sp. filaments. Together, our results show that filamentous cyanobacteria can use gliding motility to actively engineer their environments through particle collection and macrostructure formation, and that this ability is confined to a part of the filament phase space in terms of length and flexibility. These insights will allow better prediction of macrostructure formation in natural habitats and specific cyanobacterial species, and the engineering of cyanobacterial macrostructures for biotechnological applications.

biophysics↗

bioRxiv2026

Enrichment of convergent metabolic functions in microbial communities through imposed and emergent environmental niches

Microbial community composition is determined by numerous factors, including environmental filtering, biotic interactions, and stochasticity. Disentangling the relative contribution of these distinct processes is a fundamental problem for microbial ecology. Towards addressing it, here we used controlled experiments on replicate freshwater communities that vary individual factors, and used contig-based metagenomics methods to capture functional composition independently from uneven genome recovery across taxa. After repeated sub-culturing in minimal media lacking organic carbon but containing nitrate and vitamins, communities with distinct initial compositions consistently converged toward similar taxonomic structures and metabolic functions. These included oxygenic photosynthesis and nitrate metabolism, consistent with the imposed growth regime, and also showed reproducible enrichment of anoxygenic photosynthesis, vitamin biosynthesis and degradation pathways. These patterns indicate strong environmental filtering during assembly while also revealing a consistent role for emergent environments arising from microbial activity and metabolic interactions. To more directly test specific environmental drivers, we initiated replicate cultures from a single community and propagated them in the original medium and in variants lacking vitamins or both vitamins and nitrates. Only nitrate removal produced a distinct and statistically significant shift in both composition and function, with nitrate-free communities enriched for cyanobacterial nitrogen fixation and supporting metabolic functions in heterotrophs. Together, these results support a hierarchy of environmental filters determining community outcomes and provide a quantitative framework for predicting and steering community function through rational environmental design.

microbiology↗

bioRxiv2025

Safety processing shifts from hippocampal to network engagement across adolescence

Adolescence is a critical period that requires balancing exploration of uncertain and novel environments while maintaining safety. This task requires sophisticated neural integration of threat and safety cues to guide behavior. Yet little work has been conducted on threat and safety processing outside of conditioning paradigms, which, while valuable, lack the complexity to identify how the adolescent brain supports distinguishing threat from safety when both are present and as task contingencies change. In the current study, we take an approach that expands on elements of differential conditioning as well as conditioned inhibition. We recorded brain responses to external threat and self-oriented protection cues to examine how the adolescent brain supports threat-safety discrimination using 7-Tesla functional magnetic resonance imaging (fMRI). Our findings reveal an adolescent transition in the neural mechanisms supporting accurate threat-safety discrimination, with younger adolescents (12-14 years) relying predominantly on the hippocampus and older adolescents (15-17 years) utilizing a more integrated circuit involving the hippocampus and anterior ventromedial prefrontal cortex (vmPFC) connectivity. Our results clarify how competition between threat and safety cues is resolved within the visual cortex, demonstrating enhanced perceptual sensitivity to protection that is independent of threat. By examining the dynamic encoding of safety to different stimuli, the current study advances our understanding of adolescent neurodevelopment and provides valuable insights into threat-safety discrimination beyond conventional conditioning models. HighlightsO_LIProtection is more strongly weighted than threat in adolescent safety estimation. C_LIO_LIHippocampus aids accurate safety detection in younger adolescents. C_LIO_LIHippocampal-vmPFC connectivity aids accurate safety detection in older adolescents. C_LIO_LIProtection enhances visual processing, reflecting perceptual prioritization. C_LI

neuroscience↗

bioRxiv2024

Cellular (de)coordination in gliding motility and plectoneme formation

2Cyanobacteria are key contributors to biogeochemical cycles through photosynthesis and carbon fixation. In filamentous, multicellular cyanobacteria these functions can be influenced through gliding motility, which enables filaments to localise in response to light and also form aggregates. Here, we use the aggregate forming species Fluctiforma draycotensis to study gliding motility dynamics in detail. We find that filaments move in curved and straight trajectories interspersed with re-orientation or reversal of direction. Most reversals take few seconds but some take substantially longer, resulting in a long-tailed distribution of stoppage times. Mean filament speeds range around a micron per second with a relatively uniform distribution against filament length, implying that all or fixed proportion of cells in a filament contribute to movement. We implement a biophysical model that can recapitulate these findings. Model simulations show that for filaments to reverse quickly, cells in a filament must achieve high coordination of the direction of the forces that they generate. To seek experimental support of this prediction, we track individual cells in a filament. This reveals that cells translational movement is fully coupled with their rotation along the long-axis of the filament, and that cellular movement remains coordinated throughout a reversal. For some filaments, especially longer ones, however, we also find that cellular coordination can be lost, and filaments can form buckles that can twist around themselves, resulting in plectonemes. The experimental findings and the biophysical model presented here will inform future studies of individual and collective filament movement. 1 Significance StatementCyanobacteria contribute to global oxygen production and carbon capture. Some cyanobacteria exist as multicellular filaments and display gliding motility that allows them to respond to light and to form aggregates, which influences their biological functions. Here, we study the dynamics of gliding motility. We find that filaments movement is interspersed with re-orientation or reversal of direction and that mean filament speed is mostly independent of filament length. We implement a biophysical model that predicts these features to relate to cells in a filament having high coordination of the direction of the forces that they generate. We find experimental support for this predicted cellular coordination, but also discover instances of longer filaments loosing coordination, resulting in buckling and entangling with other filaments.

biophysics↗

bioRxiv2023

Identification of arginine-vasopressin receptor 1a (Avpr1a/AVPR1A) as a novel candidate gene for chronic visceral pain.

Chronic abdominal pain in the absence of ongoing disease is the hallmark of disorders of gut-brain interaction (DGBIs), including irritable bowel syndrome (IBS). While the etiology of DGBIs remains poorly understood, there is evidence that both genetic and environmental factors play a role. In this study, we report the identification and validation of Avpr1a as a novel candidate gene for visceral hypersensitivity (VH), a primary peripheral mechanism underlying abdominal pain in DGBI/IBS. Comparing two C57BL/6 (BL/6) substrains (C57BL/6NTac and C57BL/6J) revealed differential susceptibility to the development of chronic VH following intrarectal zymosan (ZYM) instillation, a validated preclinical model for post-inflammatory IBS. Using whole genome sequencing, we identified a SNP differentiating the two strains in the 5 intergenic region upstream of Avpr1a, encoding the protein arginine-vasopressin receptor 1A (AVPR1A). We used behavioral, histological, and molecular approaches to identify distal colon- specific gene expression differences and neuronal hyperresponsiveness covarying with Avpr1a genotype and VH susceptibility. While the two BL/6 substrains did not differ across other gastrointestinal (GI) phenotypes (e.g., GI motility), VH-susceptible BL/6NTac mice had higher colonic Avpr1a mRNA and protein expression. Moreover, neurons of the enteric nervous system were hyperresponsive to the AVPR1A agonist AVP, suggesting a role for enteric neurons in the pathology underlying VH. These results parallel our findings that patients colonic Avpr1a mRNA expression was higher in patients with higher pain ratings. Taken together, these findings implicate differential regulation of Avpr1a as a novel mechanism of VH-susceptibility as well as a potential therapeutic target specific to VH. SummaryA combination of approaches, from genomic analysis to functional analyses, confirm Avpr1a as a high priority candidate gene for visceral pain.

genetics↗

bioRxiv2022

Reproducible spatial structure formation and stable community composition in the cyanosphere predicts metabolic interactions

Understanding how microbial communities maintain stable compositional diversity is key for predicting community function. Studies from species pairwise interactions and synthetic communities indicate that metabolic interactions and spatial organisation can influence coexistence, but the relevance of these factors in more complex communities is unclear. Model systems often lack multi-species complexity, thereby making it difficult to study community diversity temporally. Here we used a spatially-organised cyanobacterial enrichment community to investigate compositional diversity and its stability. Over a year of passaging in media without significant carbon source, we found that the community maintains relatively high diversity, with 17 co-existing bacterial species. Using short and long read shotgun metagenomics sequencing from different time point samples, we have reconstructed complete genomes. Genomic annotation of these species revealed complementary metabolic functions involving carbon breakdown and vitamin biosynthesis suggesting interactions amongst community members. Using isolated species, we provide experimental support for carbon provision through cyanobacterial slime and growth on the component substrates by representative members of the Proteobacteria and Actinobacteriota phyla. Additionally, we experimentally show vitamin provision and uptake between prototrophic and auxotrophic members. We also found genomic capability for (an)oxygenic photosynthesis and sulfur cycling in several species. We show consistent formation of oxygen gradients across photogranule structures, supporting niches that can sustain these specific metabolic functions. These findings indicate that spatial niche formation and metabolic interactions enable maintenance of community compositional stability and diversity. SIGNIFICANCE STATEMENTMicrobes exist as species-diverse communities in nature and understanding their stability is an open challenge in microbial ecology. We established and maintained a spatially-organised, photosynthetic microbial community from a freshwater reservoir through long-term culturing in laboratory medium. We found that this community maintained a taxonomically-diverse set of 17 bacterial species. Combining genomic and physiological assays, we characterised a novel filamentous cyanobacterium capable of carbohydrate-rich slime secretion supporting growth of other microbes. We predict inter-species vitamin exchanges and identify sulfur cycling and alternative types of photosynthesis that are likely to be favoured in oxygen-free zones identified within the spatial structures. Our findings indicate that metabolic interactions and spatial structures can enable stable microbial coexistence in natural ecosystems.

microbiology↗

bioRxiv2022

Synergistic Activity of Repurposed Peptide Drug Glatiramer Acetate with Tobramycin Against Cystic Fibrosis Pseudomonas aeruginosa

Pseudomonas aeruginosa is the most common pathogen infecting the lungs of people with cystic fibrosis (CF), causing both acute and chronic infections. Intrinsic and acquired antibiotic resistance, coupled with the physical barriers resulting from desiccated CF sputum, allow P. aeruginosa to colonise and persist in spite of antibiotic treatment. As well as the specific difficulties in eradicating P. aeruginosa from CF lungs, P. aeruginosa is also subject to the wider, global issue of antimicrobial resistance. Glatiramer acetate (GA) is a peptide drug, used in the treatment of multiple sclerosis (MS), which has been shown to have moderate anti-pseudomonal activity. Other antimicrobial peptides (AMPs) have been shown to be antibiotic resistance breakers; potentiating the activities of antibiotics when given in combination restoring and/or enhancing antibiotic efficacy. Growth, viability, minimum inhibitory concentration (MIC)-determination and synergy analysis showed that GA improved the efficacy of TOB against reference strains of P. aeruginosa, reducing TOB MICs and synergising with the aminoglycoside. This was also the case for clinical strains from people with CF. GA significantly reduced the concentration of TOB required to inhibit 50% (MIC50) of viable cells (from 1.69 [95%CI 0.26-8.97] to 0.62 [95%CI 0.15-3.94] mg/L, p=0.002) and inhibit 90% (MIC90) (from 7.00 [95%CI 1.18-26.50] to 2.20 [95%CI 0.99-15.03] mg/L, p=0.001) compared with TOB-only. Investigating mechanisms of GA activity showed that GA resulted in significant disruption of outer membranes, depolarisation of cytoplasmic membranes and permeabilisation of P. aeruginosa and was the only agent tested (including cationic AMPs) to significantly affect all three.

microbiology↗

bioRxiv2021

Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated primary human airway cells

BackgroundThere are limited effective prophylactic treatments for SARS-CoV-2 infection, and limited early treatment options. Viral cell entry requires spike protein binding to the ACE2 receptor and spike cleavage by TMPRSS2, a cell surface serine protease. Targeting of TMPRSS2 by either androgen blockade or direct inhibition is already in clinical trials in early SARS-CoV-2 infection. MethodsThe likely initial cells of SARS-CoV-2 entry are the ciliated cells of the upper airway. We therefore used differentiated primary human airway epithelial cells maintained at the air-liquid interface (ALI) to test the impact of targeting TMPRSS2 on the prevention of SARS-CoV-2 infection. ResultsWe first modelled the systemic delivery of compounds. Enzalutamide, an oral androgen receptor antagonist, had no impact on SARS-Cov-2 infection. By contrast, camostat mesylate, an orally available serine protease inhibitor, blocked SARS-CoV-2 entry. However, camostat is rapidly metabolised in the circulation in vivo, and systemic bioavailability after oral dosing is low. We therefore modelled local airway administration by applying camostat to the apical surface of the differentiated ALI cultures. We demonstrated that a brief exposure to topical camostat is effective at restricting SARS-CoV-2 viral infection. ConclusionThese experiments demonstrate a potential therapeutic role for topical camostat for pre- or post-exposure prophylaxis of SARS-CoV-2, which can now be evaluated in a clinical trial.

microbiology↗