Combining machine learning and human skin explant models to harness beneficial skin microbes to treat atopic dermatitis.

Background: Atopic Dermatitis (AD) is a debilitating inflammatory skin condition that lacks a curative therapy. AD patients suffer dysbiosis of their skin microbiome, with domination by the pathogen Staphylococcus aureus, which drives immunopathology and disease progression. The extensive use of antibiotics for AD treatment has fostered the spread of antibiotic resistance, underscoring the urgent need for new therapies that can effectively combat AD and skin dysbiosis without promoting antibiotic resistance. Current AD Animal Model Drawbacks: The AD research landscape is dominated by animal models that inadequately recapitulate human disease and cause significant animal suffering. Our project aims to replace these models by integrating mathematical and machine learning models of the skin microbiome in AD with a more physiologically relevant experimental platform - a human skin explant model. PhD Project Goals: The aim of this NC3Rs PhD is to use these computational and human explant models to design and test beneficial skin microbes to eradicate Staphylococcus aureus and prevent inflammatory damage in AD. This research will achieve two significant outcomes: replacing the use of animals in AD research and developing a novel, targeted therapeutic approach that reconfigures the skin microbiome to prevent AD. We have support from labs around the world that currently use mouse models of AD who are eager to switch to our non-animal models. A Multidisciplinary Collaboration Based on a Commitment to the 3Rs: Our project is a collaboration between Dr Thomas Clarke (Department of Infectious Disease) and Prof. Reiko Tanaka (Department of Bioengineering) at Imperial College London. We will also collaborate with Dr Alex McCarthy (Department of Infectious Disease), an expert in human skin explants. Our collective expertise spans the microbiome, mathematical modelling, inflammatory and infectious disease models, and ex vivo human skin models. Our multidisciplinary team and expertise will ensure the feasibility and success of the project. Multidisciplinary Training and Support: Beyond its impact on the 3Rs and AD therapeutics, this PhD project will also provide exceptional multidisciplinary training, equipping the trainee with cutting-edge skills in the microbiome, human immunology, computational biology, and bioengineering. Our collaboration is well-established, all computational and wet lab models are in place, and we have state-of-the-art facilities. We believe our team is ideally positioned to provide the mentorship, training, and support to ensure the successful completion of this project.