Phage-inspired engineering and evolution

噬菌体启发的工程和进化

• 批准号: 10552294
• 负责人: Irene Ann Chen
• 金额: $ 38.31万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10552294
• 关键词: Address; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Biotechnology; Databases; Encapsulated; Engineering; Evolution; Exhibits; Exposure to; Goals; Gold Colloid; Knowledge; Light; Maps; Metagenomics; Organism; Peptides; Phage Display; Planet Earth; Property; Surface; Technology; Virus; experience; fitness; immunogenicity; improved; lipid nanoparticle; nanomaterials; pathogenic bacteria; Address; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Biotechnology; Databases; Encapsulated; Engineering; Evolution; Exhibits; Exposure to; Goals; Gold Colloid; Knowledge; Light; Maps; Metagenomics; Organism; Peptides; Phage Display; Planet Earth; Property; Surface; Technology; Virus; experience; fitness; immunogenicity; improved; lipid nanoparticle; nanomaterials; pathogenic bacteria

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.

项目摘要 噬菌体是感染细菌的病毒，是地球上最丰富的生物。在 此外，噬菌体是一种潜在的抗菌治疗。该项目的总体重点是噬菌体 - 激发了用于抗菌应用和基本进化研究的工程。这 第一个目标是开发针对细菌的技术的基于噬菌体的纳米材料。我们有 以前设计的合成噬菌体可输送胶体黄金，这会产生强烈的热量 暴露在光线时。这些靶向纳米材料可能有效治疗细菌 感染。但是，工程以靶向特定细菌病原体是重要的 该提案中提出的挑战。其次，噬菌体是一个绝佳的平台 进化研究，因为在其表面上显示的肽可以表现出各种功能。 根据我们以前在映射健身景观的经验，我们提出系统性 研究绘制噬菌体斑点肽的完整健身景观并探测其 可发展性。第三，为了提高功效并克服噬菌体免疫原性的问题， 我们建议在脂质纳米颗粒中封装，作为携带和 向目标传递胶体黄金。我们的方法结合了新兴的合成技术， 增长的宏基因组数据库，以及进化实证研究的进步。