Decoding Lipid–Microbiome Crosstalk Controlling Respiratory Syncytial Virus-Exacerbated Asthma

About the Project

Title: Decoding Lipid–Microbiome Crosstalk Controlling Respiratory Syncytial Virus-Exacerbated Asthma

Synopsis: To address how RSV exacerbates asthma, we will test an immunomodulatory lipid-driven gut–lung pathway in which RSV-induced eicosanoids reshape the gut microbiota, reprogramme myeloid cells, and skew lung T-cell responses, thereby amplifying chronic asthmatic inflammation and worsening disease severity.

Details: Human respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and is strongly associated with exacerbations of chronic, non-communicable airway diseases such as asthma and COPD. However, the mechanistic link between RSV infection and subsequent chronic inflammatory trajectories remain poorly defined. Beyond the airways, RSV is also associated with gastrointestinal symptoms and evidence of altered intestinal permeability and microbiome disruption. This suggest that RSV may influence respiratory outcomes via a gut-lung axis, in which inter-organ signalling during infection reprogrammes immunity in ways that shape later disease.

RSV bronchiolitis features robust eicosanoid signalling. Non-steroidal anti-inflammatory drugs (NSAIDs; e.g., aspirin, ibuprofen) are commonly used to reduce fever and discomfort by inhibiting eicosanoid production, though they do not treat RSV directly. Pre-infection ibuprofen can provide protection, and post-infection ibuprofen combined with a fusion-protein inhibitor reduced clinical severity in animal RSV models, suggesting potential disease-modifying effects. NSAIDs exert their effects primarily by inhibiting eicosanoid biosynthesis. Eicosanoids are bioactive lipid mediators with wide-ranging roles, ranging from development and homeostasis to infection-induced inflammation. By regulating differentiation and effector functions of various immune cells and epithelial cells, eicosanoids reshape tissue homeostasis, inflammatory milieu and the microbiota in both lung and gut, implicating potential mechanistic links to RSV pathogenesis and potential avenues for therapy.

This disruptive cross-disciplinary project will explore how RSV may influence asthma through gut-lung communication involving lipid mediators, the microbiome and immune programming, with the aim of identifying measurable signatures and intervention opportunities. To deliver this, we will pursue three objectives: (i) Multi-omic mapping of the RSV–eicosanoid–microbiome network and use integrative multi-modal data analyses to link this network to changes in gut mucosal function and lung immunity in RSV-exacerbated asthma; (ii) Test causality by perturbing key eicosanoid pathways and the microbiota, and relate resulting immune state changes across tissues to disease severity; and (iii) Evaluate eicosanoid- and microbiota-targeted interventions to mitigate RSV-exacerbated asthma and identify predictive lipid–microbiome–immune biomarker signatures of risk and treatment response.

Methodologically, we will employ LC–MS/MS-based lipidomics to map eicosanoid networks, microbiome sequencing with targeted metabolomics to characterise gut ecology and function, and multi-parameter immune profiling to define tissue-specific immune programmes. Targeted genetic and pharmacological perturbations and microbiota manipulations will be also employed in RSV-on-asthma mouse models. This will allow us to define mechanisms underlying infection-driven chronic non-communicable disease, identify biomarkers of exacerbation risk, and nominate host-directed or microbiota-targeted strategies to mitigate chronic disease burden. By elucidating how eicosanoid–microbiome interactions tune lung immunity during RSV, this work will provide insight into infections of humans and inform future biomarker development and host-directed strategies for chronic inflammatory airway disease.

Potential impact: This project will generate a cross-disciplinary understanding of how RSV can worsen asthma through shaping the microbiome and host immune programming across the gut-lung axis, offering intervention strategies to reduce RSV-exacerbated asthma and chronic inflammatory risk.

Training: Over the PhD, the student will follow a structured programme spanning core compliance, technical training, data analysis, communication, and career development, delivered via formal courses, hands-on mentoring. Core training will cover laboratory health and safety (COSHH, biosafety), Good Laboratory Practice, animal ethics and Home Office PIL, research integrity, data protection and sustainable lab practice. The student will gain experimental and technical expertise in lipidomics, microbiome workflows, in vivo animal models, transgenic colony management, gut barrier assays, multicolour flow cytometry, molecular biology, and confocal/multiplex imaging. Data training includes data management and FAIR practice, experimental design and statistics, bioinformatics for RNA-seq and microbiome sequencing, integrative data analysis and visualisation. The student will develop communication skills through academic writing, regular poster and oral presentations at lab/centre seminars, external conferences, and public (patient) engagement.

Career development includes an individual development plan, opportunities for authorship and exposure to peer review, conferences and networking, short placements and/or lab exchanges with collaborators, grant writing from travel/small awards to fellowship applications, leadership and positive research culture (EDI, local committees), enterprise commercialisation support, and access to university-supported careers workshops. Teaching experience includes co-supervising undergraduate/MSc projects and contributing to course activities, and support toward teaching accreditation where available. Collectively, this PhD will equip the student with a rigorous interdisciplinary skill set for careers in academia, industry, clinical/translational research, or science communication.

Recruitment: An Upper Second Class (2:1) degree or above in Biology, Biomedical Sciences, Immunology, Infectious Diseases, or a related field.

Apply: All applications must be submitted through the Future Medicine PhD fellowships website.