Human Skin Microbiome Engineering

ended

The skin microbiome constitutes an attractive platform to incorporate novel functionalities to the host, due to accessible location, tight contact with the host, low immunogenicity, and easier genetic manipulation, among other reasons. I will adopt a translational synthetic biology approach to engineer the human skin commensal C. acnes (formerly P. acnes) as a disease-sensing biological device (“biodevice”) with therapeutic activity. Precisely, engineered C. acnes will detect atopic dermatitis (AD, the most common chronic inflammatory disease worldwide) and respond by producing an anti-inflammatory molecule. First, I will develop a vector and a methodology for efficient gene delivery into C. acnes. Next, I will construct synthetic gene circuits that will allow C. acnes to detect inflammatory markers in vitro and to respond by secreting anti-inflammatory signals. Finally, I will use the C. acnes biodevice as an in vivo therapeutic product: I will apply the engineered bacteria on a mouse model of AD and evaluate its potential as a therapeutic tool capable of disease-sensing and regulated maintenance of skin homeostasis. This project will contribute to the emerging field of human microbiome genetic engineering, will inspire and guide future efforts towards microbiome repurposing for therapeutics, and has the potential to provide exploitable results and better therapeutic options for AD patients.