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Signaling Hierarchies in Vertebrate Development

Award Number: P01HD022486
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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DESCRIPTION (provided by applicant): Diagnosis and treatment of many genetic diseases is hindered by variation in disease symptoms. The reasons for this variation are often unknown because systematic studies have not been undertaken. The goal of this Program Project is to elucidate mechanisms underlying normal phenotypic resilience and the instability that occurs when such mechanisms are lost in the disease state. We hypothesize that variation can result from failure of mechanisms that normally buffer against noise in developmental processes, for example stochastic variation in gene activities and cellular read-outs, and thus assure phenotypic stability in healthy children. We test this hypothesis in three Projects (Projects), using the zebrafish, a premiere model organism pioneered by this group at the University of Oregon. The projects take advantage of attributes of the zebrafish for developmental genetics analyses, including exquisite time-lapse microscopy of transgenically labeled fish to follow developmental events and perturbations in real time, assays of macromolecular complex formation, genome-wide analyses of cell signaling events, and assessment of environmental interactions that modulate host gene expression. These studies will elucidate the nature of events leading to variability in disease symptoms. Project1 focuses on variation In Fraser syndrome, a rare inherited disorder characterized by craniofacial and pharyngeal epithelial disruptions that show a remarkable degree of variation, both among affected individuals and on the left and right sides of the same individual. Proposed studies will explore how failure of epithelial-mesenchymal interactions results in differences in craniofacial skeletal development and will reveal genes responsible for the stability and resilience seen under normal conditions. Project2 tests a novel hypothesis for phenotypic variation with Usher syndrome, the most prevalent cause of hereditary deaf-blindness, hypothesizing that it results from disruption of complexes of Usher proteins that cause cellular stress that leads to stochastic cell death. Project3 investigates phenotypic variation associated with Hirschsprung disease, the leading cause of intestinal aganglionosis, exploring the hypothesis that the enteric nervous system regulates composition of intestinal bacterial communities and that altered communities contribute to disease progression by promoting inflammation and amplifying intestinal motility defects. Together with support of four Core Units, this Program Project will provide novel insights into three specific diseases and develop a new understanding of the mechanisms underlying disease variability that will promote better disease diagnosis and treatment.


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: 2020 ( Subtotal = -$103,692 )
2020	2017	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	30	1/28/2020	NON-COMPETING CONTINUATION	-$103,692
														Subtotal = -$103,692

Issue Date FY: 2017 ( Subtotal = $1,983,290 )
2017	2017	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	007	30	8/24/2017	NON-COMPETING CONTINUATION	$1,551,696
2017	2015	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	006	28	10/28/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,270,556
2017	2015	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	005	28	10/28/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,270,556
2017	2014	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	002	27	10/28/2016	NON-COMPETING CONTINUATION	$1,508,248
2017	2014	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	003	27	10/28/2016	NON-COMPETING CONTINUATION	$1,508,248
2017	2014	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	004	27	10/28/2016	NON-COMPETING CONTINUATION	-$431,592
2017	2013	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	26	10/28/2016	COMPETING CONTINUATION	$193,901
2017	2013	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	001	26	10/28/2016	COMPETING CONTINUATION	$193,901
														Subtotal = $1,983,290

Issue Date FY: 2016 ( Subtotal = $3,044,426 )
2016	2016	UNIVERSITY OF OREGON	POST OFFICE BOX 3237	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	29	8/17/2016	NON-COMPETING CONTINUATION	$1,536,178
2016	2015	UNIVERSITY OF OREGON	POST OFFICE BOX 3237	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	002	28	9/14/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2016	2014	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	001	27	9/14/2016	NON-COMPETING CONTINUATION	$1,508,248
														Subtotal = $3,044,426

Issue Date FY: 2015 ( Subtotal = $4,656 )
2015	2015	UNIVERSITY OF OREGON	POST OFFICE BOX 3237	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	28	9/3/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,512,904
2015	2014	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	001	27	9/3/2015	NON-COMPETING CONTINUATION	-$1,508,248
														Subtotal = $4,656

Issue Date FY: 2014 ( Subtotal = $1,508,248 )
2014	2014	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	27	8/6/2014	NON-COMPETING CONTINUATION	$1,508,248
														Subtotal = $1,508,248

Issue Date FY: 2013 ( Subtotal = $1,581,913 )
2013	2013	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	26	9/17/2013	COMPETING CONTINUATION	$1,581,913
														Subtotal = $1,581,913

Issue Date FY: 2011 ( Subtotal = $1,877,249 )
2011	2011	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	25	8/11/2011	NON-COMPETING CONTINUATION	$1,877,249
														Subtotal = $1,877,249

Issue Date FY: 2010 ( Subtotal = $1,944,090 )
2010	2010	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	002	24	6/21/2010	NON-COMPETING CONTINUATION	$1,896,550
2010	2010	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Trans-NIH Recovery Act Research Support	001	23	4/14/2010	SUPPLEMENT FOR EXPANSION	$47,540
2010	2009	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Trans-NIH Recovery Act Research Support	000	22	11/23/2009	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,944,090

Issue Date FY: 2009 ( Subtotal = $1,907,441 )
2009	2009	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Trans-NIH Recovery Act Research Support	000	22	6/3/2009	SUPPLEMENT FOR EXPANSION	$47,540
2009	2009	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	001	23	7/8/2009	NON-COMPETING CONTINUATION	$1,859,901
														Subtotal = $1,907,441

Issue Date FY: 2008 ( Subtotal = $1,712,726 )
2008	2008	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	22	6/24/2008	NON-COMPETING CONTINUATION	$1,712,726
														Subtotal = $1,712,726

Issue Date FY: 2007 ( Subtotal = $1,693,061 )
2007	2007	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	21	8/3/2007	COMPETING CONTINUATION	$1,693,061
														Subtotal = $1,693,061

Issue Date FY: 2006 ( Subtotal = $1,891,970 )
2006	2006	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	20	7/21/2006	NON-COMPETING CONTINUATION	$1,891,970
														Subtotal = $1,891,970

Issue Date FY: 2005 ( Subtotal = $1,822,531 )
2005	2005	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	19	2/10/2005	NON-COMPETING CONTINUATION	$1,822,531
														Subtotal = $1,822,531

Issue Date FY: 2004 ( Subtotal = $1,791,433 )
2004	2004	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	18	2/10/2004	NON-COMPETING CONTINUATION	$1,791,433
														Subtotal = $1,791,433

Issue Date FY: 2003 ( Subtotal = $1,718,289 )
2003	2003	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	17		NON-COMPETING CONTINUATION	$1,718,289
														Subtotal = $1,718,289

Issue Date FY: 2002 ( Subtotal = $1,672,681 )
2002	2002	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	16	7/18/2002	COMPETING CONTINUATION	$1,672,681
														Subtotal = $1,672,681

Issue Date FY: 2001 ( Subtotal = $1,535,065 )
2001	2001	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	15	2/21/2001	NON-COMPETING CONTINUATION	$1,535,065
														Subtotal = $1,535,065

Issue Date FY: 2000 ( Subtotal = $1,530,139 )
2000	2000	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Child Health and Human Development Extramural Research	000	14	1/24/2000	NON-COMPETING CONTINUATION	$1,530,139
														Subtotal = $1,530,139

Issue Date FY: 1999 ( Subtotal = $1,446,945 ) (Continued on the next page)
Grand Total All Awards = $32,004,762

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Signaling Hierarchies in Vertebrate Development

Award Number: P01HD022486

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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