Thursday, November 21, 2024 11/21/2024

Administrative Supplements for Equipment Purchases for R35GM129294 Regulation of mitochondrial surveillance

Award Number: R35GM129294
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Summary: Far from the overly simplistic understanding of mitochondria as ‘the powerhouse of the cell’, these organelles play crucial roles not only in the production of ATP, but also in a wide variety of other biochemical processes, making mitochondrial function a key determinant of cellular health. Disruption of mitochondrial homeostasis contributes to a number of chronic diseases, including metabolic, neurodegenerative, and cardiovascular disorders, cancer, and even aging. Mitochondria undergo constant surveillance and homeostatic rebalancing to avoid spiraling into a dysfunctional cascade that will inevitably trigger apoptosis or other cell death pathways. A variety of readouts, including mitochondrial proteostasis and bioenergetics, are constantly tracked and these inputs are integrated into coherent, retrograde signaling programs that coordinate gene expression with the nucleus. The most studied of these is the mitochondrial unfolded protein response (UPRmt), which primarily responds to compromised mitochondrial protein import. Recent results from my lab have increasingly demonstrated that another key component of mitochondrial surveillance is the ESRE pathway. The ESRE (ethanol and stress response element) pathway is comprised of evolutionarily-conserved genes containing a strongly conserved, 11-nucleotide motif (TCTGCGTCTCT) in their promoters. These genes were first identified by their upregulation during acute ethanol exposure, but we have demonstrated that the ESRE pathway detects mitochondrial damage, specifically increased mitochondrial reactive oxygen species. Importantly, compromised ESRE function reduced survival during stress and overexpression of ESRE machinery extended lifespan in unstressed conditions. Recent discoveries from my lab have identified box C/D snoRNPs and the Mediator subunit MDT-15/MED15 as critical regulators of ESRE activity. Finally, we have identified a strong candidate for the transcription factor that binds the ESRE motif. Despite our recent progress, critical gaps remain in our understanding of how ESRE contributes to mitochondrial health. Questions of particular interest include: how is the signal for ESRE activation propagated to the nucleus once it is detected? Have we correctly identified the transcription factor that binds the ESRE motif? What is the mechanism used by box C/D snoRNPs to regulate ESRE function? Is MDT-15 acting in a non-canonical role to regulate ESRE activity? We will continue to use a variety of biochemical, genetic, and cell biological techniques, supplemented with new ‘omics-based approaches to expand our understanding of this network and its role in maintaining mitochondrial health. This enhanced understanding will be key to translating our discoveries into tangible gains in improvements in health across the lifespan.


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 = $0 )
2025	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	002	6	11/6/2024	COMPETING CONTINUATION	$38,876
2025	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	6	11/5/2024	COMPETING CONTINUATION	$0
2025	2022	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	001	5	11/6/2024	NON-COMPETING CONTINUATION	-$38,876
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $601,148 )
2024	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	002	6	8/21/2024	SUPPLEMENT FOR EXPANSION	$125,829
2024	2024	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	001	6	1/31/2024	COMPETING CONTINUATION	$475,319
2024	2022	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	5	1/23/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $601,148

Issue Date FY: 2022 ( Subtotal = $384,615 )
2022	2022	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	5	8/12/2022	NON-COMPETING CONTINUATION	$384,615
														Subtotal = $384,615

Issue Date FY: 2021 ( Subtotal = $451,304 )
2021	2021	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	002	4	8/27/2021	SUPPLEMENT FOR EXPANSION	$56,404
2021	2021	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	3	5/27/2021	SUPPLEMENT FOR EXPANSION	$10,285
2021	2021	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	001	4	8/26/2021	NON-COMPETING CONTINUATION	$384,615
														Subtotal = $451,304

Issue Date FY: 2020 ( Subtotal = $463,582 )
2020	2020	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	2	6/5/2020	SUPPLEMENT FOR EXPANSION	$11,281
2020	2020	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	001	3	8/17/2020	NON-COMPETING CONTINUATION	$452,301
														Subtotal = $463,582

Issue Date FY: 2019 ( Subtotal = $384,615 )
2019	2019	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	2	8/21/2019	NON-COMPETING CONTINUATION	$384,615
														Subtotal = $384,615

Issue Date FY: 2018 ( Subtotal = $384,615 )
2018	2018	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	1	8/23/2018	NEW	$384,615
														Subtotal = $384,615

Grand Total All Awards = $2,669,879

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Administrative Supplements for Equipment Purchases for R35GM129294 Regulation of mitochondrial surveillance

Award Number: R35GM129294

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer