Phage-inspired engineering and evolution

NIH Pandemic-Era Grants

Pandemic Era Grants

2023

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Principal Investigator: Irene Ann Chen
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2023
Award: $383,143
Funding agency: National Institute of General Medical Sciences

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.

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