Monday, February 16, 2026 2/16/2026

Genome Architecture and Gene Control in Response to Stress

Award Number: R01GM138988
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: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Genome Architecture and Gene Control in Response to Stress - 1 Project Summary 2 3 The 3D topology of the genome plays a critical role in transcriptional regulation in health, disease and 4 development. While techniques such as Hi-C and ChIA-PET have revealed static views of global genome 5 architecture, very little is known about the mechanisms that control dynamic topological rearrangements. We 6 have established a system in budding yeast – the Hsf1-mediated heat shock response – in which concerted 7 structural rearrangements within and between a set of specific target genes take place. During heat shock, 8 Hsf1 drives its target genes dispersed on different chromosomes to undergo striking changes in conformation 9 and coalesce into discrete, transcriptionally active foci. These Hsf1 target genes encode a dedicated group of 10 protein homeostasis (proteostasis) factors. Through their regulation, the human orthologue of Hsf1 (hHSF1) 11 has been suggested to be a clinical target in malignant cancers and in neurodegenerative diseases. Thus, this 12 proposal has dual significance: it will both elucidate mechanisms that control chromatin conformational 13 dynamics and reveal how Hsf1 coordinates expression of the proteostasis machinery. 14 The Hsf1-mediated heat shock response in budding yeast represents an ideal model system to investigate 15 the regulation and function of 3D genome rearrangements for two reasons: 1) The magnitude, rapidity and 16 specificity of the intra- and intergenic rearrangements are all unprecedented and thus represent exciting, novel 17 biology; and 2) It will allow us to leverage the power of yeast gene-tics to dissect the mechanisms and define 18 the functional relevance of genome topology dynamics. 19 Aim 1 will investigate the 3D rearrangements that occur genome-wide during heat shock and the role 20 played by Hsf1 and RNA polymerase II (including its CTD phosphorylation state) in orchestrating specific and 21 robust interchromosomal contacts. The experiments will use primarily ChIA-PET approaches. 22 Aim 2 will focus deeply on the role of Hsf1 binding sites and its functional domains in underpinning its 23 ability to dynamically drive members of its regulon into coalesced intranuclear foci. 24 Aim 3 will test the role of Mediator and other cofactors - transcriptional co-activators, chromatin remodelers 25 and architectural proteins - in driving HSP gene coalescence and investigate the possibility that HSP gene 26 coalescence represents a condensate that assembles through liquid-liquid phase separation. 27 In support of the NIH mission, the precedents established in this proposal will inform therapeutic efforts 28 aimed broadly at 3D genome regulation and may suggest novel molecular handles with which to modulate 29 Hsf1 and the proteostasis machinery to treat cancer and neurodegenerative diseases.


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 = $0 )
2026	2023	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Biomedical Research and Research Training	000	4	1/20/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $326,150 )
2023	2023	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Biomedical Research and Research Training	000	4	6/15/2023	NON-COMPETING CONTINUATION	$292,000
2023	2023	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Biomedical Research and Research Training	001	4	7/19/2023	SUPPLEMENT FOR EXPANSION	$34,150
														Subtotal = $326,150

Issue Date FY: 2022 ( Subtotal = $292,000 )
2022	2022	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Biomedical Research and Research Training	000	3	6/2/2022	NON-COMPETING CONTINUATION	$292,000
														Subtotal = $292,000

Issue Date FY: 2021 ( Subtotal = $292,000 )
2021	2021	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Biomedical Research and Research Training	000	2	5/21/2021	NON-COMPETING CONTINUATION	$292,000
														Subtotal = $292,000

Issue Date FY: 2020 ( Subtotal = $320,000 )
2020	2020	LOUISIANA STATE UNIVERSITY	1501 KINGS HWY	SHREVEPORT	LA	71103	CADDO	USA	Biomedical Research and Research Training	000	1	7/22/2020	NEW	$320,000
														Subtotal = $320,000

Grand Total All Awards = $1,230,150

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Genome Architecture and Gene Control in Response to Stress

Award Number: R01GM138988

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: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer