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Mechanisms of gene regulation in bacterial defense islands

Award Number: F31AI194603
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Mechanisms of gene regulation in bacterial defense islands - PROJECT SUMMARY Mechanisms of gene regulation in bacterial defense islands Advancements in bioinformatics and the availability of tens of thousands of bacterial genome sequences have enabled the discovery of diverse pathways in bacteria that defend against environmental stress and bacteriophage (phage) infection. Over 100 different antiphage immune systems have been identified, and each bacterial genome encodes a different combination of ~5-20 such systems. Over the past five years, the molecular mechanisms of many antiphage immune systems have been deciphered, but because immune systems are typically studied one-by-one in model organisms, how these systems are regulated in their native hosts is not well understood. Our lab previously identified the transcriptional regulators CapH+CapP and CapW, which are each associated with diverse antiphage immune systems and control their expression in response to phage infection and/or DNA damage. Our fortuitous discovery of CapH+CapP and CapW implies that many similar regulators remain to be discovered. The aim of my research is to identify and characterize novel transcriptional regulators associated with antiphage immune systems in clinically-important bacterial pathogens. While studying ubiquitination-related BilABCD and BubABCD systems, I identified the novel transcriptional regulators CapK and CapS, and further found that these proteins co-occur with a variety of antiphage immune systems. I will define the upstream signal(s) and molecular mechanisms of CapK+CapS, thereby expanding our knowledge of how bacteria respond to phage infection. Building off my work on CapK+CapS, I will perform comprehensive bioinformatics searches of bacterial genomes to identify new immune system-associated transcriptional regulators, then use my established experimental workflow to validate their activity and define their molecular mechanisms. Complementing this work, I will perform gene expression profiling (RNA-Seq) on a large panel of clinical Enterobacter isolates with distinct sets of antiphage immune systems, to determine whether and how these systems are regulated in response to phage infection, DNA damage, and other stress. This work will define the global transcriptional control networks that regulate expression of antiphage immune systems and coordinate the bacterial response to infection. Together, the work proposed here will comprehensively define the mechanisms of transcriptional regulation in antiphage immune systems, and establish gene expression regulation as a widespread means of bacterial immune system control.


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 = $46,939 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	8/12/2026	NON-COMPETING CONTINUATION	$46,939
														Subtotal = $46,939

Issue Date FY: 2025 ( Subtotal = $45,982 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	1	7/17/2025	NEW	$0
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	$45,982
														Subtotal = $45,982

Grand Total All Awards = $92,921

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Mechanisms of gene regulation in bacterial defense islands

Award Number: F31AI194603

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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