Latest Publications

Niamh E. Harrington​, Freya Allen​, Ramón Garcia Maset and Freya Harrison

The opportunistic pathogen Pseudomonas aeruginosa forms biofilm infections in the lungs of people with the genetic condition cystic fibrosis (CF) that can persist for decades. There are numerous P. aeruginosa lifestyle changes associated with chronic biofilm infection that are cued by the CF lung environment. These include a loss of virulence, metabolic changes and increased antimicrobial tolerance. We have investigated P. aeruginosa PA14 biofilm infection over 7 days in an ex vivo pig lung (EVPL) model for CF, previously shown to facilitate formation of a clinically relevant P. aeruginosa biofilm structure with expression of key genes comparable to human infection. We have compared P. aeruginosa gene expression between sequential time points: 24 h, 48 h and 7 days post-infection, and investigated tolerance to polymyxins. Our results demonstrate that the EVPL model can maintain a P. aeruginosa biofilm population, which exhibits increased antibiotic tolerance, for at least 7 days. Differential expression of antimicrobial resistance-associated genes was not observed; however, there was significant upregulation of sulphur metabolism and maintenance of a structured biofilm. Our findings demonstrate that 7 days is a viable time point for studying established, chronic biofilm infection in the EVPL model and provide insight into the accompanying gene expression changes.

Microbiology, March 2026

Wanqing Jiang, Cecilia Skoug, Ian Rodrigues, Ernesto Ciabatti, Fiona M. Gribble, Frank Reimann, Daniel I. Brierley, Marie K. Holt, Stefan Trapp

Glucagon-like peptide-1 receptor (GLP-1R) activation in the brain strongly reduces appetite, but most brain GLP-1Rs are not accessible for systemically administered GLP-1R agonists. Acute activation of nucleus tractus solitarius (NTS) GLP-1 neurons, known as preproglucagon (PPG) neurons, strongly suppresses food intake separate from GLP-1R agonists. However, it is unknown if chronic stimulation of PPG neurons is a viable strategy for appetite suppression, or if obesity disrupts their function. Here we demonstrate that PPG neurons in the NTS and intermediate reticular nucleus (IRT) determine meal size, and that their total number is inversely correlated with bodyweight gain. We report that PPG^NTS and PPG^IRT neurons receive distinct monosynaptic inputs, but have convergent efferent projection targets throughout the brain, and that combined ablation of both populations delays the onset of physiological satiation to a degree sufficient to promote weight gain under ad libitum chow fed conditions. Crucially, chronic daily chemogenetic activation of PPG^NTS+IRT neurons drives robust and sustained hypophagia and weight loss in obese mice without notable adverse effects, demonstrating their value as targets for obesity pharmacotherapy.

Molecular Metabolism, May 2026

Daniela M Riley, Randa Elsayed, Mark D Walsh, Simaran Johal, Ying Lin, Harry Walton, Till Bretschneider, Sascha Ott, Andrew C Nelson

Although vertebrate species are superficially diverse, they share key commonalities in terms of overall morphology, as well as organ configuration and function. Maintenance of these traits during evolution is partially explained by the conservation of critical genes governing embryonic development. However, for conserved genes to deliver consistent developmental outcomes between species, similar gene regulatory programs and gene expression patterns must also be maintained. The endoderm germ layer makes major contributions to the respiratory and gastrointestinal tracts and to associated organs including the liver and pancreas. We used functional genomic approaches to identify highly conserved endodermal cis-regulatory modules (CRMs) functioning across the 400 million years of evolution separating zebrafish and humans. Our analyses suggest that there are few endoderm-specific CRMs, with many CRMs governing pancreas development also likely acting within the nervous system. Furthermore, these highly conserved CRMs are strongly enriched for binding sites of “neuro-pancreatic” transcription factors governing both pancreas and nervous system development, potentially suggesting function across these distinct organ systems. Additionally, we identify highly conserved CRMs potentially participating in endodermal patterning of adjacent craniofacial structures and sensory tissues. The highly conserved CRMs we identify are characterized by conserved patterns of transcription factor binding site co-occurrence. However, rigid arrangement of binding sites is not a common characteristic of the identified CRMs, suggesting more complex or individual grammatical rules. Overall, our analyses provide key insights into critical gene regulatory control during vertebrate endoderm organogenesis and define a compendium of highly conserved CRMs that should be prioritized for analysis of neuro-pancreatic gene transcriptional control and of anterior embryonic patterning.

Genome Research, March 2026

Vasthi Alonso Chávez, Nathan Brown, Stephen Parnell, Matt Coombes, Alison Dyke, Clare Hall, Berglind Karlsdóttir, Mariella Marzano, Joanne Morris, Liz O'Brien, David Williams, Alice E. Milne

• Across the world, emerging pests and diseases are increasing in number, range and co-occurring with other invasive biotic factors. Ash trees (Fraxinus excelsior L.; Oleaceae) in Great Britain face the potential invasion of the emerald ash borer (EAB; Agrilus planipennis Fairmaire; Coleoptera: Buprestidae) and the ongoing impact of ash dieback (ADB; Hymenoscyphus fraxineus T. Kowalski (Helotiales: Helotiaceae)). Surveillance and management strategies accounting for land manager behaviour are crucial for improved control.
• We developed a spatially explicit model that integrates (i) the estimated prevalence of ADB, (ii) the dynamics of EAB arrival and spread and (iii) a socio-dynamics model, based on a values-driven theory that simulates land manager decision-making in relation to surveillance and tree management. In the model, if EAB is detected, contingency measures—including tree felling and intensified monitoring—are enacted, with the potential to eradicate or slow its spread. We used the model to assess whether targeting high-risk sites with traps, using routine tree inspections by land managers, or encouraging volunteer surveillance (with or without subsidised trapping) could significantly slow EAB spread.
• Interviews (n=45), a survey (n=368), and three workshops (n=27) informed the socio-dynamics model's structure and parameterisation. The interaction between EAB and ADB is complex, with potential positive effects (e.g. increased perceived value of ash) and negative effects (e.g. belief that ash cannot be saved, misidentification of decline causes).
• Results showed that if land managers are made aware of EAB, health and safety inspections have a substantial role to play in slowing the spread but are unlikely to lead to eradication due to the pest's cryptic larval phase. Official trapping at a limited number of locations is similarly unlikely to succeed in early detection and eradication unless entry pathways are well-defined, and ash connectivity is low. Volunteer trapping is important for early detection and if this is subsidised, EAB eradication becomes more likely.
• Synthesis and applications. Tree-health policies must balance identifying likely entry points and deployment of traps, targeted information campaigns and surveillance subsidies for land managers. Our unique, cross-disciplinary approach can be applied to other pest/pathogen systems to inform tree-health plans and how to balance resources.

Journal of Applied Ecology, March 2026

Christopher James O’Grady, Sally Hilton, Emma Picot, Sebastien Raguideau 2, Christopher Quince, Christopher J. van der Gast, Hendrik Schaefer, Gary D. Bending

Biological soil crusts (BSCs) are formed by phototrophic organisms at the soil surface and play a key role in structuring microbial communities and biogeochemical processes in dryland ecosystems. Similar surface associated communities occur in temperate agricultural soils, but their development, assembly dynamics and functional significance remain poorly understood. We investigated the temporal development of the soil surface microbiome following tillage and during subsequent growth of a winter wheat crop, integrating multi-kingdom amplicon sequencing with metagenomic analysis to track phototrophic, bacterial, fungal and protist communities, together with co-amplified macroscopic phototrophs. Distinct surface communities of phototrophs, bacteria and protists established rapidly, within 4 weeks of tillage, and underwent marked succession from early dominance by yellow-green algae (Xanthophyceae) to cyanobacteria, charophytes and ultimately mosses. Across all taxonomic groups, community assembly at the soil surface increasingly shifted towards dispersal limitation over time, whereas bulk soil communities were predominantly shaped by ecological drift. By the end of the growing season, the soil surface had developed a functional profile distinct from bulk soil, characterised by a greater representation of photosynthetic processes, largely due to eukaryotic algal carbon fixation, alongside increased genetic potential for heterotrophic carbon, nitrogen, phosphorus and sulphur cycling. These functional shifts were associated with enrichment of Actinobacteria, Bacteroidetes and Proteobacteria. Our results demonstrate that the soil surface of temperate agricultural systems represents a dynamic and functionally differentiated microbial habitat, which shares key biological features with dryland BSCs while exhibiting distinct functional and successional trajectories, revealing an overlooked component of managed temperate ecosystems.

Soil Biology and Biochemistry, June 2026

Roisin Murphy, Julia A. Fairbairn, Becca W.A. Baileeves, Phillip J. Stansfeld, Timothy D.H. Bugg

A series of 4-aryl-2-imidazoles containing an ortho-substituted benzyl substituent were designed as a new peptidomimetic scaffold for an Arg-Trp-x-x-Trp motif used by lysis protein E from bacteriophage ϕX174 to target translocase MraY on the peptidoglycan biosynthesis pathway. The analogues showed antimicrobial activity against a panel of ESKAPE pathogens, with compound 9c (substituent CF₃) showing effective antimicrobial activity against antibiotic-resistant Acinetobacter baumannii 19606 (MIC 8 μg/mL) and Staphylococcus aureus MRSA USA300 (MIC 8 μg/mL). The analogues showed 33–47% inhibition of particulate E. coli MraY at 200 μM concentration, with highest enzyme inhibition shown by compound 9b (substituent F, IC₅₀ 210 μM). Docking against the structure of E. coli MraY revealed a possible binding site in the “elbow” of bent helix 9, close to Phe-288. This work identifies the MraY-protein E interaction site as a possible target for the antimicrobial activity of bromoageliferin, and establishes a new skeleton for design of non-nucleoside MraY inhibitors.

Bioorganic & Medicinal Chemistry Letters, July 2026