Monday, June 30, 2025 6/30/2025

Bacteriophage interactions with enteric pathogens

Award Number: R35GM140803
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Bacteriophage interactions with enteric pathogens - Project Summary How phages and viruses recognize their specific host cell receptors is not known for the vast majority of species. The long-term goal is to understand the general principles behind the structures and mechanisms that control host cell entry for bacteriophages. The objective of this proposal is to determine the structures, and mechanisms of how phages use both outer and inner membrane proteins for infection in enteric pathogens such as Shigella, E.coli and Salmonella. The central hypothesis is that there are conserved protein structures and corresponding mechanisms that govern phage entry for the majority of phage:host pairs. We predict that there are universal cell surface features that are generally required for phage entry, and also other cell surface features that may be specific to individual phage:host pairs. The rationale underlying the proposed work is that we will identify key receptor proteins in enteric pathogens that mediate phage infection, and that a better understanding of these interactions will provide physical targets for either identifying new therapies or improving existing ones. We will pursue this research using a combination of conceptual and technological innovations involving genetics, biochemistry and biophysics. These include innovations recently developed in my laboratory, as well as more established microbiological techniques. The proposed research is significant, as it will provide both structural and mechanistic insights into how phages dock to their specific hosts, a necessary step for productive infection. This work will also develop resources that will be used by other researchers. For example, the proposed work will develop widely-applicable complex transposon and single gene deletion libraries, which will greatly propel research forward in Shigella, as currently no such genetic toolkit exists. The expected outcome of this work will provide a basic understanding of how phages attach to hosts including which proteins and interactions are universally required, and which are specific to individual phage:host pairs. Additionally, we will gain an atomic level understanding of the protein:protein binding interactions and transient infection intermediate states that control infection. Atomic level details, such as how phages bind to their hosts are critical for engineering new therapeutics or enhancing existing ones.


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: 2025 ( Subtotal = $385,721 )
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	001	5	4/7/2025	NON-COMPETING CONTINUATION	$385,721
2025	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	4	11/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $385,721

Issue Date FY: 2024 ( Subtotal = $385,721 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	4	3/18/2024	NON-COMPETING CONTINUATION	$347,149
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	001	4	7/15/2024	NON-COMPETING CONTINUATION	$38,572
														Subtotal = $385,721

Issue Date FY: 2023 ( Subtotal = $385,721 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	3	5/8/2023	NON-COMPETING CONTINUATION	$385,721
														Subtotal = $385,721

Issue Date FY: 2022 ( Subtotal = $385,721 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	2	3/21/2022	NON-COMPETING CONTINUATION	$347,148
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	001	2	6/27/2022	NON-COMPETING CONTINUATION	$38,573
														Subtotal = $385,721

Issue Date FY: 2021 ( Subtotal = $496,721 )
2021	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	1	4/29/2021	NEW	$496,721
														Subtotal = $496,721

Grand Total All Awards = $2,039,605

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Bacteriophage interactions with enteric pathogens

Award Number: R35GM140803

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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