Monday, June 30, 2025 6/30/2025

Mechanisms of Embryo Response to Oxidative Stress

Award Number: R01ES016366
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2009
PERIOD OF PERFORMANCE END DATE: 09/30/2015

Group Awards By:

View Award Description

Mechanisms of Embryo Response to Oxidative Stress - Project Summary/Abstract Oxidative stress resulting from environmental exposures is associated with a variety of human diseases ranging from chemical teratogenesis to cardiovascular and neurodegenerative diseases. Developing animals appear to be especially sensitive to chemicals causing oxidative stress. The expression and inducibility of anti- oxidant defenses are critical factors affecting susceptibility to oxidants at these early life stages, but the ontogenic development of these responses in embryos is not well understood. In adult animals, oxidants initiate an anti-oxidant response by activating NF-E2-related factor 2 (NRF2) and related proteins, which bind to the anti-oxidant response element and activate transcription of genes such as glutathione S-transferases, NAD(P)H-quinone oxidoreductase, glutamyl-cysteine ligase, and superoxide dismutase. The overall objective of the research proposed here is to elucidate the mechanisms by which vertebrate embryos respond to oxidative stress during development. We will test the central hypothesis that responsiveness to oxidative stress and the set of regulated genes vary during development. Because of these developmental differences, some stages may be more sensitive to oxidative stress-induced damage. These studies will be performed in vivo using embryos of the zebrafish (Danio rerio), a valuable model in which to examine mechanisms of toxicity in developing animals and to screen chemicals for developmental toxicity. Aim 1 will use transcriptional profiling and phenotypic anchoring to identify the core set of genes that comprise the oxidative stress response in embryos, establish how the responsiveness and composition of the core set of oxidant-responsive genes vary with developmental stage of embryos, and determine how the timing and gene profile of the oxidative stress response differ in embryos exposed to structurally and mechanistically distinct activators of NRF2 (tBHQ, diquat, sulforaphane). Aim 2 will elucidate the roles of different NRF paralogs in the transcriptional response to oxidative stress during development in embryos in vivo, using targeted knock-down of NRF protein synthesis with morpholino oligonucleotides. Aim 3 will establish the mechanism of regulation of anti-oxidant response genes during embryonic development through computational and in vivo experimental analysis of oxidant-responsive gene promoters, leading to the generation of a stable line of transgenic zebrafish expressing a reporter gene (GFP) in response to oxidative stress. Finally, we will test a set of mammalian developmental toxicants for the ability to activate the transgene in embryos. The results of these studies will establish the composition and ontogeny of the transcriptional response to oxidative stress in vertebrate embryos, elucidate fundamental mechanisms underlying this response, generate tools for screening chemicals for activity as developmental toxicants or antioxidants, and provide insight into the role of oxidative stress in human disease.


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: 2015 ( Subtotal = $0 )
2015	2013	WOODS HOLE OCEANOGRAPHIC INSTITUTE	MS # 14 CHALLENGER HOUSE	WOODS HOLE	MA	02543	BARNSTABLE	USA	Environmental Health	000	5	3/11/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $369,211 )
2013	2013	WOODS HOLE OCEANOGRAPHIC INSTITUTE	MS # 14 CHALLENGER HOUSE	WOODS HOLE	MA	02543	BARNSTABLE	USA	Environmental Health	000	5	4/12/2013	NON-COMPETING CONTINUATION	$339,072
2013	2013	WOODS HOLE OCEANOGRAPHIC INSTITUTE	MS # 14 CHALLENGER HOUSE	WOODS HOLE	MA	02543	BARNSTABLE	USA	Environmental Health	001	5	7/4/2013	NON-COMPETING CONTINUATION	$30,139
														Subtotal = $369,211

Issue Date FY: 2012 ( Subtotal = $370,788 )
2012	2012	WOODS HOLE OCEANOGRAPHIC INSTITUTE	MS # 14 CHALLENGER HOUSE	WOODS HOLE	MA	02543	BARNSTABLE	USA	Environmental Health	000	4	3/28/2012	NON-COMPETING CONTINUATION	$370,788
														Subtotal = $370,788

Issue Date FY: 2011 ( Subtotal = $380,708 )
2011	2011	WOODS HOLE OCEANOGRAPHIC INSTITUTE	MS # 14 CHALLENGER HOUSE	WOODS HOLE	MA	02543	BARNSTABLE	USA	Environmental Health	000	3	3/17/2011	NON-COMPETING CONTINUATION	$346,097
2011	2011	WOODS HOLE OCEANOGRAPHIC INSTITUTE	MS # 14 CHALLENGER HOUSE	WOODS HOLE	MA	02543	BARNSTABLE	USA	Environmental Health	001	3	6/13/2011	NON-COMPETING CONTINUATION	$34,611
														Subtotal = $380,708

Issue Date FY: 2010 ( Subtotal = $378,367 )
2010	2010	WOODS HOLE OCEANOGRAPHIC INSTITUTE	MS # 14 CHALLENGER HOUSE	WOODS HOLE	MA	02543	BARNSTABLE	USA	Environmental Health	000	2	3/23/2010	NON-COMPETING CONTINUATION	$378,367
														Subtotal = $378,367

Issue Date FY: 2009 ( Subtotal = $376,190 )
2009	2009	WOODS HOLE OCEANOGRAPHIC INSTITUTE	MS # 14 CHALLENGER HOUSE	WOODS HOLE	MA	02543	BARNSTABLE	USA	Environmental Health	000	1	6/8/2009	NEW	$376,190
														Subtotal = $376,190

Grand Total All Awards = $1,875,264

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of Embryo Response to Oxidative Stress

Award Number: R01ES016366

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2009

PERIOD OF PERFORMANCE END DATE: 09/30/2015

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer