HuSME | Human Skin Microbiome Engineering

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/882387
Start date: 01-12-2020
End date: 30-11-2022
Total budget - Public funding: 160 932,48 Euro - 160 932,00 Euro
Cordis data

Original description

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.

Status

TERMINATED

Call topic

MSCA-IF-2019

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2019
MSCA-IF-2019