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ATP-driven detection of foreign proteins triggers diverse mechanisms of cellular defense and phage-mediated counter defense

Award Number: R35GM134867
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ATP-driven detection of foreign proteins triggers diverse mechanisms of cellular defense and phage-mediated counter defense - PROJECT SUMMARY Viruses are generally considered to be agents of destruction that must be efficiently eliminated by the host for self-preservation. However, viruses are also the largest reservoir of genetic diversity on the planet, and viral infections (estimated 1023 infections per second) are a primary mechanism for delivering new genes to naïve hosts. Thus, viruses have a complex role in the process of evolution, being both a major source of disease and mortality, while simultaneously presenting the cellular community with new opportunities for genetic innovation. In bacteria, viruses (i.e., phages) are major purveyors of genes that confer virulence and antibiotic resistance, and thus play a major role in the evolution of bacterial pathogenesis. The long-term goal of our research is to understand the impact of phage defense systems on the evolution and ecology of human-associated microbial communities, while also identifying and prioritizing research aimed at understanding immune systems that are conserved across domains of life. Specifically, the work outlined in this proposal will determining the phylogenetic and functional diversity of ATP-driven immune systems in bacteria, and how these systems recognize diverse viral proteins. We use bioinformatics and phylogenetics to guide structural, biological, and biochemical experiments to determine how foreign proteins are recognized, how detection of antigenic proteins trigger the activation of diverse immune effectors that block viral infection, and how viruses escape protection by these systems. Results from this research will add fundamental new insights to our understanding of the mechanism of viral defense, help explain the origins and evolution of immune systems, and may lead to new mechanistic insights that can be creatively repurposed for applications in human health.


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 = $582,105 )
2025	2025	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	002	6	5/7/2025	COMPETING CONTINUATION	$582,105
2025	2024	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	000	5	11/6/2024	NON-COMPETING CONTINUATION	$0
2025	2024	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	001	5	4/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $582,105

Issue Date FY: 2024 ( Subtotal = $537,366 )
2024	2024	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	001	5	6/28/2024	NON-COMPETING CONTINUATION	$53,735
2024	2024	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	000	5	12/13/2023	NON-COMPETING CONTINUATION	$483,631
														Subtotal = $537,366

Issue Date FY: 2023 ( Subtotal = $633,034 )
2023	2023	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	002	4	6/1/2023	SUPPLEMENT FOR EXPANSION	$95,668
2023	2023	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	000	4	1/5/2023	NON-COMPETING CONTINUATION	$483,631
2023	2023	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	001	4	3/23/2023	NON-COMPETING CONTINUATION	$53,735
														Subtotal = $633,034

Issue Date FY: 2022 ( Subtotal = $537,366 )
2022	2022	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	001	3	7/25/2022	NON-COMPETING CONTINUATION	$53,736
2022	2022	MONTANA STATE UNIVERSITY	216 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	000	3	1/19/2022	NON-COMPETING CONTINUATION	$483,630
														Subtotal = $537,366

Issue Date FY: 2021 ( Subtotal = $515,893 )
2021	2021	MONTANA STATE UNIVERSITY, INC	211 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	000	2	1/25/2021	NON-COMPETING CONTINUATION	$464,306
2021	2021	MONTANA STATE UNIVERSITY, INC	211 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	001	2	3/4/2021	NON-COMPETING CONTINUATION	$51,587
														Subtotal = $515,893

Issue Date FY: 2020 ( Subtotal = $404,074 )
2020	2020	MONTANA STATE UNIVERSITY, INC	307 MONTANA HALL	BOZEMAN	MT	59717	GALLATIN	USA	Biomedical Research and Research Training	000	1	1/31/2020	NEW	$404,074
														Subtotal = $404,074

Grand Total All Awards = $3,209,838

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ATP-driven detection of foreign proteins triggers diverse mechanisms of cellular defense and phage-mediated counter defense

Award Number: R35GM134867

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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