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Enhancing bacteriophage function with coevolution and synthetic biology

Award Number: K08AI187778
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/17/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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Enhancing bacteriophage function with coevolution and synthetic biology - Project Summary/Abstract: Antimicrobial resistance (AMR) poses a growing threat to human health, with nearly 5 million deaths worldwide attributed to AMR bacterial infections in 2019. There is a growing critical need for innovative treatments for AMR infection, and phage therapy, which uses naturally occurring viruses that attack bacteria, is emerging as a potentially powerful treatment modality. Phage therapy is limited by the ability of bacteria to evolve resistance to phages, but phages have the capacity to evolve counter-resistance. We do not fully understand the diversity of ways that phage can evolve to overcome a wide variety of bacterial resistance strategies. The overall objective of this proposal is to use experimental evolution in the laboratory to identify genetic changes in phages that are responsible for enhanced phage function, and to engineer phages that have optimized traits to suppress bacterial growth. The experiments in specific aim 1 will examine the genetic and functional patterns underlying enhanced phage function when phage T2 is evolved alongside a variety of diverse clinical isolates of Escherichia coli. The experiments in specific aim 2 will identify the causative mutations in evolved phages, their optimal combinations, and the associated mechanisms of action. This work will contribute new insights to phage-bacteria interactions that will assist in the design of engineered phage therapies, as well as collections of genetically and functionally characterized evolved and engineered phages with enhanced antibacterial function. This proposal is designed to support the career development of the candidate, who will expand expertise in the microbiology of bacteria and phages, microbial genomics, and experimental methods in synthetic biology. The proposed work is expected to identify new mechanisms that phages can exploit to overcome bacterial resistance, providing the groundwork for the candidate to develop independent lines of research.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $200,846 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	2	6/22/2026	NON-COMPETING CONTINUATION	$200,446
2026	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	1/6/2026	NEW	$400
														Subtotal = $200,846

Issue Date FY: 2025 ( Subtotal = $197,646 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	7/17/2025	NEW	$197,646
														Subtotal = $197,646

Grand Total All Awards = $398,492

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Enhancing bacteriophage function with coevolution and synthetic biology

Award Number: K08AI187778

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/17/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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