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Uncovering key regulators for the Mitochondrial Ethanol and Stress Response Element and elucidating their role in host defense

Award Number: F31AI203007
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/23/2026
PERIOD OF PERFORMANCE END DATE: 08/22/2029

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Uncovering key regulators for the Mitochondrial Ethanol and Stress Response Element and elucidating their role in host defense - Project Summary Antimicrobial resistance is a growing global health threat, and improved strategies to understand and bolster host defense mechanisms are urgently needed. Many pathogens damage mitochondria to subvert innate immune signaling, yet the mechanisms by which hosts detect and respond to pathogen-induced mitochondrial stress remain poorly defined. The Caenorhabditis elegans Ethanol and Stress Response Element (ESRE) pathway is an evolutionarily conserved mitochondrial surveillance system that is activated by reactive oxygen species and mitochondrial damage during bacterial pathogenesis. Disruption of ESRE activity decreases host survival during Pseudomonas aeruginosa pathogenesis, indicating that ESRE is critical for host defense against this pathogen. However, the regulatory network controlling ESRE activation and the mechanistic role of ESRE regulators in host defense remain unknown. The key focus of this project is to define how transcription factors and kinases regulate ESRE activation and determine how these regulators shape host responses to multiple bacterial pathogens. Achieving this goal will uncover the molecular mechanisms governing ESRE regulation and establish their connection with innate immunity during bacterial pathogenesis. Aim 1 will identify regulators of the ESRE pathway using an RNAi screen of transcription factors and kinases with a 3XESRE::GFP reporter and will determine their specificity by testing their effects on UPRmt, MAPKmt, UPRER, and mitophagy using transcriptional reporters and qRT-PCR. Chromatin immunoprecipitation will test whether specific regulators bind the conserved 11-nucleotide ESRE motif. Aim 2 will define how ESRE regulators influence host survival during P. aeruginosa, Staphylococcus aureus, and Enterococcus faecalis infection in liquid- and agar-based pathogenesis models. RNA-seq, mitochondrial functional assays, and ROS quantification will identify ESRE-dependent transcriptional responses and determine how mitochondrial health correlates with survival outcomes. The regulatory hierarchy connecting ESRE repressors such as ELT-3 and ZIP-11 with box C/D snoRNPs and PMK-1/p38 innate immune signaling will also be elucidated. By identifying and explaining how hosts sense and respond to pathogen-induced mitochondrial damage, this project advances fundamental understanding of infectious disease biology and innate immunity. These insights directly support the NIAID’s mission to expand knowledge of infectious and immunologic diseases and to enable the development of strategies that improve host resilience against emerging and drug-resistant pathogens.


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 = $50,114 )
2026	2026	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Allergy and Infectious Diseases Research	001	1	8/1/2026	NEW	$0
2026	2026	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Allergy and Infectious Diseases Research	000	1	8/1/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Uncovering key regulators for the Mitochondrial Ethanol and Stress Response Element and elucidating their role in host defense

Award Number: F31AI203007

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/23/2026

PERIOD OF PERFORMANCE END DATE: 08/22/2029

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