Microbial Drivers of Oronasal Mucosal Melanoma: Spatial Mapping, Mechanistic Insights, and Clinical Relevance

• Prof Kelly Blacklock, Kelly.blacklock@ed.ac.uk
• Prof Liz Patton, E.patton@ed.ac.uk
• Dr Mark Stares, Mark.stares@ed.ac.uk
• Prof Crispin Miller, Crispin.Miller@glasgow.ac.uk 

Application deadline

30^th June 2025

Funding information (students eligible to apply) 

UK & International students

The CRUK Scotland Centre studentships are for 4 years and provide an annual tax-free stipend of £22,113 + 1.75% indexation in Year 2,3&4, university tuition fees and a consumables budget. 

Students will be registered for their degree at either the University of Glasgow or Edinburgh, depending on the project they apply for. This scheme is open to both UK and international applicants. 

https://www.crukscotlandcentre.ac.uk/training/phd-studentships

Project description

Oronasal mucosal melanoma (OMM) is a rare and aggressive malignancy with limited treatment options beyond surgery. Unlike cutaneous melanoma, which has benefited from substantial research and therapeutic advances, rare melanomas such as OMM remain understudied and underfunded. Consequently, OMM patients face poorer outcomes, fewer treatment options, and are less likely to be enrolled in clinical trials. Moreover, most knowledge of melanoma is derived from patients of European descent, where public health measures have reduced mortality. In contrast, OMM is more common in other populations and is not associated with ultraviolet (UV) exposure, indicating distinct disease mechanisms. Notably, patients from non-European backgrounds tend to have a worse prognosis than their counterparts of European descent. Further research is essential to address these disparities, uncover the underlying risk factors, and develop tailored therapies and public health strategies for all patient populations.

The aetiopathogenesis of OMM is not well understood, but our most recent work showed, for the first time, that the local microbiome may play a significant role in modulating tumour progression and metastasis1. 

The Objective of this project is to investigate how the oronasal microbiome interacts with host tissues and influences tumour behaviour. This may facilitate development of novel treatment options, or biomarkers of progression or treatment response. 

In collaboration with NHS boards across Scotland, we have established a pan-Scotland cohort of archival OMM tissue from over 100 patients, complete with extensive clinical records, including patient sex, age and ethnicity. This provides a rich resource for linking molecular findings with clinical outcomes.

Aim 1: Mapping the Spatial Host-Microbiome Interactome in OMM

Recent advances in spatial transcriptomics offer an unprecedented opportunity to map the molecular crosstalk between host tissues and microbial communities within the tumour microenvironment. The first phase of this project will employ cutting-edge technologies, such as Stereo-seq, to generate high-resolution 3D maps that visualise microbial localisation and host gene expression in archived OMM tissues. By integrating spatial transcriptomic data of the tumour and peri-tumour regions with detailed clinical records, we aim to identify specific microbial communities linked to distinct tumour behaviours and progression patterns, providing new insights into disease mechanisms.

Aim 2: Investigating Microbial Influence Using Patient-Derived Organoid Models

The second phase will involve leveraging our established patient-derived organoid models to replicate tumour-microbe interactions under controlled conditions. These models will enable detailed investigations into how key microbial species identified in Phase 1 impact tumour behaviours, such as proliferation, invasion, and migration. Comprehensive transcriptomic analyses will reveal microbial-induced alterations in host gene expression and signalling pathways, shedding light on potential mechanisms driving disease progression.

Aim 3: Evaluating Microbiome Profiles as Predictors of Clinical Outcomes

In the final phase, we will evaluate the clinical relevance of the oronasal microbiome by profiling microbial communities in a pan-Scotland cohort of OMM patients. Longitudinal sampling and correlation with clinical outcomes will help identify microbiome-based biomarkers predictive of recurrence and treatment response. 

Collaborating with industry partners (e.g. GambitBio), we will explore the development of rapid, at-home microbiome testing solutions to enable continuous monitoring and early intervention.

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