Thursday, November 21, 2024 11/21/2024

Hair Bundle Proteins

Award Number: R01DC002368
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary This project’s long-term objective is to elucidate mechanisms that control hair-bundle development and function, show how defects in these mechanisms cause deafness and vestibular disorders, and identify pathways that could be modulate to ameliorate these syndromes. Because the ability to control bundle development may assist in hair-cell regeneration strategies, our project aims to uncover the mechanisms a hair cell uses to regulate and modulate steps in bundle growth. Although our past work focused on postnatal development of bundles of apical inner hair cells (IHCs) from the mouse cochlea, here we expand our scope here to include embryonic development, outer hair cells (OHCs), and hair cells from apex to base of the cochlea. In the first Aim, we will collect (and share) datasets of stereocilia actin and key row-specific proteins for IHCs from mid cochlear regions to the base and OHCs from apex to base. Our goal is to discern the broad developmental plan for cochlea bundles, and to identify the steps that individual hair cells modulate to create the distinct arrangements of stereocilia in these diverse bundles. In the second Aim, we will characterize the first stage of stereocilia growth, stage II in Tilney’s categorization, by measuring stereocilia dimensions, determining locations and concentrations of key proteins, and revealing the presence of interstereocilia links during embryonic development. Importantly, we will use mouse mutants to determine roles for the tip-link cadherins CDH23 and PCDH15, as well as the molecular motors MYO15A, MYO7A, MYO3A, and MYO3B. In the final Aim, we address how the pattern of stereocilia arrangement on the hair cell’s apical surface is determined. Our hypothesis is that spacing is initially set when stereocilia grow during stage II; as they are tightly packed together then with their spacing set by stereocilia width, their pattern is set and stabilized by growth of the rootlets and their interconnections through rootlet-rootlet filaments and the cuticular plate. Mice lacking ANKRD24, GRXCR2, MYO7A, or SPTAN1 have substantially altered stereocilia packing in mature hair cells, suggesting that these four proteins—and likely many others—participate in setting stereocilia spacing.


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	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	001	29	11/1/2024	COMPETING CONTINUATION	$33,044
2025	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	28	11/1/2024	NON-COMPETING CONTINUATION	-$33,044
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $599,920 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	002	29	7/3/2024	COMPETING CONTINUATION	$599,920
2024	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	28	6/4/2024	NON-COMPETING CONTINUATION	$0
2024	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	001	28	6/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $599,920

Issue Date FY: 2022 ( Subtotal = $477,667 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	28	6/13/2022	NON-COMPETING CONTINUATION	$477,667
														Subtotal = $477,667

Issue Date FY: 2021 ( Subtotal = $477,667 )
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	27	6/15/2021	NON-COMPETING CONTINUATION	$477,667
														Subtotal = $477,667

Issue Date FY: 2020 ( Subtotal = $477,667 )
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	26	6/16/2020	NON-COMPETING CONTINUATION	$477,667
														Subtotal = $477,667

Issue Date FY: 2019 ( Subtotal = $479,820 )
2019	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	002	25	6/11/2019	NON-COMPETING CONTINUATION	$479,820
2019	2018	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	001	24	11/30/2018	COMPETING CONTINUATION	$104,964
2019	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	23	11/30/2018	NON-COMPETING CONTINUATION	-$104,964
														Subtotal = $479,820

Issue Date FY: 2018 ( Subtotal = $489,015 )
2018	2018	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	24	6/2/2018	COMPETING CONTINUATION	$489,015
														Subtotal = $489,015

Issue Date FY: 2017 ( Subtotal = $386,015 )
2017	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	23	6/19/2017	NON-COMPETING CONTINUATION	$386,015
														Subtotal = $386,015

Issue Date FY: 2016 ( Subtotal = $386,015 )
2016	2016	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	22	6/14/2016	EXTENSION WITH OR WITHOUT FUNDS	$386,015
														Subtotal = $386,015

Issue Date FY: 2015 ( Subtotal = $382,156 )
2015	2015	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	21	6/12/2015	NON-COMPETING CONTINUATION	$382,156
														Subtotal = $382,156

Issue Date FY: 2014 ( Subtotal = $386,015 )
2014	2014	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	20	6/17/2014	NON-COMPETING CONTINUATION	$386,015
														Subtotal = $386,015

Issue Date FY: 2013 ( Subtotal = $386,015 )
2013	2013	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	19	6/28/2013	COMPETING CONTINUATION	$386,015
														Subtotal = $386,015

Issue Date FY: 2011 ( Subtotal = $494,483 )
2011	2011	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	18	6/23/2011	NON-COMPETING CONTINUATION	$494,483
														Subtotal = $494,483

Issue Date FY: 2010 ( Subtotal = $497,925 )
2010	2010	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	17	6/17/2010	NON-COMPETING CONTINUATION	$497,925
														Subtotal = $497,925

Issue Date FY: 2009 ( Subtotal = $588,308 )
2009	2009	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Trans-NIH Recovery Act Research Support	000	15	7/15/2009	SUPPLEMENT FOR EXPANSION	$100,000
2009	2009	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97239	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	001	16	6/16/2009	NON-COMPETING CONTINUATION	$488,308
														Subtotal = $588,308

Issue Date FY: 2008 ( Subtotal = $474,087 )
2008	2008	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	15	6/17/2008	NON-COMPETING CONTINUATION	$474,087
														Subtotal = $474,087

Issue Date FY: 2007 ( Subtotal = $466,341 )
2007	2007	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	14	6/14/2007	COMPETING CONTINUATION	$466,341
														Subtotal = $466,341

Issue Date FY: 2006 ( Subtotal = $424,648 )
2006	2006	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	13	6/16/2006	NON-COMPETING CONTINUATION	$424,648
														Subtotal = $424,648

Issue Date FY: 2005 ( Subtotal = $422,204 )
2005	2005	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	12	6/23/2005	NON-COMPETING CONTINUATION	$422,204
														Subtotal = $422,204

Issue Date FY: 2004 ( Subtotal = $409,905 )
2004	2004	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	11	5/24/2004	NON-COMPETING CONTINUATION	$409,905
														Subtotal = $409,905

Issue Date FY: 2003 ( Subtotal = $397,967 )
2003	2003	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	10	6/13/2003	NON-COMPETING CONTINUATION	$397,967
														Subtotal = $397,967

Issue Date FY: 2002 ( Subtotal = $406,910 )
2002	2002	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK ROAD	PORTLAND	OR	97201	MULTNOMAH	USA	Research Related to Deafness and Communication Disorders	000	9	7/2/2002	COMPETING CONTINUATION	$406,910
														Subtotal = $406,910

Grand Total All Awards = $10,661,016

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Hair Bundle Proteins

Award Number: R01DC002368

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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