- Identification of Key Chemokines and Markers: Integration of patient metagenomic and transcriptomic data has revealed microbial gene clusters and immune factors that strongly correlate with AD severity.
- In Silico Modelling: Computational models reproduce healthy versus disease states and predict how engineered SSMDs with antioxidant or antimicrobial functions may restore balance. Simulations also suggest that periodic dosing of SSMDs is likely required to overcome competition with native CA strains, providing key design rules for future application.
- Dynamic Interplay Between Skin and Microbial Species: New in silico and in vitro studies demonstrate how CA–SA interactions drive skin health or disease states, reinforcing the significance of developing SSMDs to aid in skin recovery and fulfil the project’s objective of innovative AD treatment.
- Genetic Toolkit for C. acnes: A versatile and stable engineering platform has been established, including genome integration (“landing pad”), CRISPRi, recombinases, and surface display systems. Novel endogenous sensors (e.g. for tryptophan, vitamin B12, oxidative stress) and synthetic regulators have been implemented, expanding the possibilities for precise sensing and therapeutic delivery.
- Enhanced Bacterial Strains: Prototype SSMD strains with therapeutic activity have been created and genome-integrated to ensure stability. These include antioxidant-secreting strains, immune-modulatory prototypes (IL-4R blocking), and bacteriocin-producing candidates targeting S. aureus.
- Bacterial Interactions: Using stratum corneum and epidermal equivalent models, the consortium is able to track competition, colonisation, and therapeutic effects under AD-like conditions.
- 3D Skin Models: Human epidermal equivalents (HEEs) and advanced AD skin models were refined to stably mimic lesional and non-lesional disease phenotypes. Minimal synthetic microbiomes composed of CA, SA, S. epidermidis, and C. striatum have been established, enabling reproducible investigations of microbial dynamics in disease-relevant environments.
- Bacterial Engraftment and RNA Analysis: Methodologies for engrafting live bacteria onto skin models have been validated, and new workflows for microbial RNA isolation and ciRNAseq are under development. These methods will allow simultaneous monitoring of host and microbial transcriptional responses, creating a powerful platform for understanding therapeutic action.
- Biocontainment Strategies: First-generation auxotrophic C. acnes strains have been successfully generated and tested in syntrophic combinations, showing potential as safety layers for future therapeutic application.
In regard to dissemination and communication, the plan implemented by the SKINDEV project ensures consistency and visibility across all published articles. Guidelines, including publication standards, are established to maintain uniformity and quality in disseminating research findings to the scientific community and the general public.
To further amplify the project’s visibility, UPF has taken the lead in producing promotional and outreach materials, while multiple partners have published peer-reviewed papers, delivered conference presentations, and engaged in public-facing activities. Together, these efforts strengthen SKINDEV’s impact and pave the way for translation, commercialisation, and regulatory uptake of its results.
