Phage-inspired engineering and evolution

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Project Summary Phages are viruses that infect bacteria, and are the most abundant type of organism on earth. In addition, phages are a potential antibacterial therapy. The overall focus of the project is phage- inspired engineering for antibacterial applications and fundamental evolutionary studies. The first goal is to develop phage-based nanomaterials for technologies targeting bacteria. We have previously engineered synthetic phages to deliver colloidal gold, which creates intense heat when exposed to light. These targeted nanomaterials may be effective for treating bacterial infections. However, engineering them to target a specific bacterial pathogen is an important challenge that is addressed in this proposal. Second, phages are an excellent platform for evolutionary studies, as peptides displayed on their surfaces can exhibit various functions. Based on our previous experience with mapping fitness landscapes, we propose systematic studies to map the complete fitness landscape of phage-displayed peptides and probe their evolvability. Third, to improve efficacy and overcome problems with immunogenicity of phages, we propose encapsulation in lipid nanoparticles as an alternative approach for carrying and delivering colloidal gold to a target. Our approaches combine emerging synthetic technologies, growing metagenomic databases, and advances in empirical studies of evolution.