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Epigenetic Regulation of Diapause in Culex pipiens: The Roles of H3K27me2/3 and H3K27ac

Award Number: R15AI139861
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Epigenetic Regulation of Diapause in Culex pipiens: The Roles of H3K27me2/3 and H3K27ac - Project Summary/Abstract In temperate climates, the mosquito Culex pipiens overwinters in a dormant state known as adult diapause—a crucial survival strategy that enables persistence through cold seasons and facilitates the overwintering of pathogens such as West Nile virus. Despite the public health significance of diapause, the molecular mechanisms regulating this adaptive program remain poorly understood. Our preliminary work implicates histone post-translational modifications (hPTMs), particularly H3K27 methylation (H3K27me2/3) and acetylation (H3K27ac), as critical regulators of gene expression during diapause. These chromatin modifications likely function downstream of the insulin/Foxo signaling axis to mediate metabolic suppression, reproductive arrest, and stress tolerance. This proposal aims to dissect the epigenetic framework governing diapause in Cx. pipiens, focusing on how specific histone modifications regulate gene networks involved in overwintering physiology. In Aim 1, we will identify H3K27me2/3 target genes using ChIP-seq and functionally validate them via DIPA-CRISPR, assessing impacts on lipid metabolism and survival. Aim 2 investigates the antagonistic role of H3K27ac using genome-wide occupancy data and single-cell RNA sequencing to reveal how dynamic chromatin remodeling establishes diapause-specific transcriptional programs. In Aim 3, we will manipulate histone deacetylase (HDAC) activity through RNAi and pharmacological inhibition to determine how reduced HDAC expression enhances H3K27ac levels and diapause-like traits. We will employ state-of-the-art techniques including solid-state NMR, FTIR spectroscopy, single-cell transcriptomics, and genome editing. The integration of metabolic and chromatin profiling will provide unprecedented insights into how environmental cues reprogram mosquito physiology through epigenetic regulation. Importantly, the work targets diapause as a seasonal bottleneck in mosquito life history—an underexploited window for vector control intervention. By elucidating the epigenetic basis of diapause, this project will reveal regulatory targets that can be disrupted to impair overwintering success, potentially reducing mosquito abundance and disease risk in early transmission seasons. These findings will also advance broader understanding of environmental adaptation via epigenetic mechanisms in invertebrates.


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 = $516,916 )
2026	2026	BAYLOR UNIVERSITY	700 S UNIVERSITY PARKS DR	WACO	TX	76706	MCLENNAN	USA	Allergy and Infectious Diseases Research	000	3	5/26/2026	COMPETING CONTINUATION	$516,916
														Subtotal = $516,916

Issue Date FY: 2024 ( Subtotal = -$4,847 )
2024	2023	BAYLOR UNIVERSITY	700 S UNIVERSITY PARKS DR	WACO	TX	76706	MCLENNAN	USA	Allergy and Infectious Diseases Research	000	2	10/1/2023	COMPETING CONTINUATION	-$4,847
														Subtotal = -$4,847

Issue Date FY: 2023 ( Subtotal = $443,169 )
2023	2023	BAYLOR UNIVERSITY	700 S UNIVERSITY PARKS DR	WACO	TX	76706	MCLENNAN	USA	Allergy and Infectious Diseases Research	002	2	6/27/2023	COMPETING CONTINUATION	$10,914
2023	2023	BAYLOR UNIVERSITY	700 S UNIVERSITY PARKS DR	WACO	TX	76706	MCLENNAN	USA	Allergy and Infectious Diseases Research	000	2	11/14/2022	COMPETING CONTINUATION	$443,169
2023	2018	BAYLOR UNIVERSITY	700 S UNIVERSITY PARKS DR	WACO	TX	76706	MCLENNAN	USA	Allergy and Infectious Diseases Research	001	1	6/27/2023	NEW	-$10,914
														Subtotal = $443,169

Issue Date FY: 2018 ( Subtotal = $346,250 )
2018	2018	BAYLOR UNIVERSITY	700 S UNIVERSITY PARKS DR	WACO	TX	76706	MCLENNAN	USA	Allergy and Infectious Diseases Research	000	1	5/1/2018	NEW	$346,250
														Subtotal = $346,250

Grand Total All Awards = $1,301,488

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Epigenetic Regulation of Diapause in Culex pipiens: The Roles of H3K27me2/3 and H3K27ac

Award Number: R15AI139861

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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