Naturalising wound repair: how microbial diversity shapes immune resolution of skin injury

Precision Medicine Project - Naturalising wound repair: how microbial diversity shapes immune resolution of skin injury

Supervisor(s): Dr Iris Mair, Assistant Prof Sofia Ferreira-Gonzalez, Prof Amy Pederson, Prof Kathryn Else [University of Manchester]
Centre/Institute: Institute of Immunology and Infection Research

Background

Chronic, non-healing skin wounds such as diabetic foot and venous leg ulcers affect around 200,000 UK patients and represent a major economic burden for the NHS, estimated at £5.6 billion annually. The incidence has doubled since 2012, reflecting UK's growing burden of diabetes and cardiovascular disease associated with health inequalities. Mouse models of wound healing are a cornerstone for understanding factors that impact the wound healing process and for developing novel therapeutics. However, most mechanistic insights derive from specific-pathogen-free (SPF) laboratory mice whose restricted microbiota and environmental exposure result in an 'immature' immune system resembling that of a newborn rather than an adult human (Beura et al. Nature 2016, DOI: 10.1038/nature17655). 

A regulated immune response, shaped by skin microbial cues and other environmental factors, is critical for successful wound healing. For wounds not to become chronic, the immune response must undergo a precisely-timed transition from an initial inflammatory to a resolution phase (Eming et al. Science 2017, DOI: 10.1126/science.aam7928). Recent 'naturalisation' studies demonstrate that introducing wild mouse microbiota matures the mouse immune system and dramatically improves concordance with human vaccine and infection responses (Rosshart et al. Science 2019, DOI: 10.1126/science.aam7928). However, the effects of diverse, wild mouse microbiota on skin wound healing and underlying immune responses remain unexplored. 

We have access to a unique study system of wild house mice on the Isle of May (Scotland, UK), having studied their immune system over the past 8 years (Mair et al. PLOS Pathogens 2024, DOI: 10.1371/journal.ppat.1012119). Preliminary flow-cytometric analysis of ear skin tissue reveals altered immune cell composition, activation and metabolic state in wild versus laboratory mice. This PhD project will investigate microbial diversity effects on skin immunity and wound repair using banked tissues and metadata from (i) wild house mice, (ii) germ-free mice re-colonised with wild-mouse or SPF microbiota, and (iii) SPF mice 'naturalised' with wild-mouse microbiota.

Aims

  1. Map transcriptomic, histological and immune profiles of skin tissue from mice with distinct microbial exposure histories 

    The student will use snRNA-seq to analyse ear skin at day 0, 3 and 7 following injury across SPF laboratory, naturalised, and wild mice to determine how microbial diversity impacts inflammatory-to-resolution progression. Histological analysis will assess differences in healing progression across groups. Intact and wounded ear skin samples from ca. 160 wild mice will be used to investigate environmental/host drivers of variation in baseline immune states and healing success, identifying ‘fast’ and ‘slow’ healers. Datasets will be compared against existing human wound healing transcriptomic atlases to identify signatures in wild or naturalised mice that better match human wound healing progression

  2. Define microbial signatures associated with enhanced wound repair

    Using 16S rRNA sequencing of skin samples from the wild and wild-to-lab wound healing experiments, the student will determine whether microbial diversity and composition correlate with immune states and healing outcomes. Multivariate modelling will integrate microbiome composition, host factors and immune profiles to identify predictive signatures of successful wound repair.

  3. Investigate spatial localisation and functionally validate key immune mediators identified through transcriptomic analysis

    The student will perform immunofluorescence analysis on skin tissue sections to understand cellular and mediator localisation patterns that distinguish fast from slow healing responses. Functional validation of promising bacterial or immune mediators of enhanced wound healing will be performed using in vitro wound healing scratch assays, with the potential to establish skin explant assays or organoid cultures for 3D analyses.

Training outcomes

The student will become proficient in advanced immunological and computational techniques spanning wet and dry lab skills. Laboratory skills will include tissue processing for histology, immunofluorescence and snRNA-seq, qPCR, and in vitro wound healing assays. They will learn snRNA-seq and microbiome analysis using established bioinformatics pipelines, and become proficient in R for statistical analysis and multivariate modelling to identify signatures predictive of wound healing outcomes. This training will provide a comprehensive understanding of precision medicine strategies applied to chronic inflammatory diseases, positioning the student for careers in academic research, pharmaceutical development, or clinical applications focused on personalised medicine.

Apply Now

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  • The deadline for 26/27 applications is Monday 12th January 2026
  • Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
  • Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.  

Q&A Sessions

Supervisor(s) of each project will be holding a 30 minute Q&A session in the first two weeks of December. 

If you have any questions regarding this project, you are invited to attend the session on TBC via Microsoft Teams. Click here to join the session.

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