Thursday, November 21, 2024 11/21/2024

Intracellular Calcium in Hair Cells

Award Number: R01DC001362
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/ABSTRACT The main objective of the proposed experimental program is to address questions of mechanotransducer (MET) channel structure and function employing a combination of electrophysiological and genetic techniques. Experiments will focus on the attributes and molecular composition of the hair cell MET channel complex, gathering more evidence that transmembrane channel-like protein isoform TMC1 forms a central component of the channel and dictates its biophysical properties. Hair cell responses will be measured in acutely isolated cochleae of wild-type and mutant mice. Specific aims are: (1) to record and characterize the conductance and ionic properties of MET channels in cochlear hair cells of different mice, each with a distinct Tmc1 missense mutation. The site of the mutations will be selected to define the location of the channel pore, the residues differing between TMC1 and TMC2, and those determining channel block by Ca2+. (2) Using mutations of the accessory protein LHFPL5 to define its contribution to channel conductance, gating and adaptation. One hypothesis is that LHFPL5 provides force transmission between the tip link and the MET channel. (3) To investigate the time course of loss of MET currents and transduction in Tmc1 mutants during the third postnatal week and explore underlying mechanisms. All mutants display MET currents up to postnatal day 12 but lose them over the subsequent five to ten days depending on the mutant. One hypothesis to be tested is that decreased Ca2+ entry into the hair bundle is a major determinant of loss of transduction and that differences between mutants reflect differences in steady Ca2+ influx. The connection between reduced hair bundle Ca2+, lipid scrambling, and hair cell death will also be explored. (4) Determine the origin of a new type of Ca2+ dependent force generation that we previously observed in gecko hair cells. It is hypothesized that this same process exists in mammalian vestibular hair cells. The roles in the process of the kinocilium and non-muscle myosins NMIIB and NMIIC at the endolymphatic surface of the hair cell around the cuticular plate will be studied. It is hoped that the results will supply evidence on the molecular makeup of the hair cell transduction apparatus and yield information about proteins that are mutated in certain forms of human genetic deafness.


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	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	33	10/10/2024	COMPETING CONTINUATION	$309,915
2025	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	32	10/10/2024	NON-COMPETING CONTINUATION	-$309,915
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $623,903 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	33	2/28/2024	COMPETING CONTINUATION	$623,903
2024	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	32	2/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $623,903

Issue Date FY: 2023 ( Subtotal = $510,327 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	32	12/20/2022	NON-COMPETING CONTINUATION	$459,295
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	32	1/13/2023	NON-COMPETING CONTINUATION	$51,032
														Subtotal = $510,327

Issue Date FY: 2022 ( Subtotal = $510,327 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	31	4/22/2022	NON-COMPETING CONTINUATION	$51,033
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	31	12/15/2021	NON-COMPETING CONTINUATION	$459,294
														Subtotal = $510,327

Issue Date FY: 2021 ( Subtotal = $509,523 )
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	30	12/16/2020	NON-COMPETING CONTINUATION	$458,571
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	30	1/8/2021	NON-COMPETING CONTINUATION	$50,952
														Subtotal = $509,523

Issue Date FY: 2020 ( Subtotal = $536,095 )
2020	2020	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	29	12/17/2019	NON-COMPETING CONTINUATION	$482,485
2020	2020	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	29	1/17/2020	NON-COMPETING CONTINUATION	$53,610
														Subtotal = $536,095

Issue Date FY: 2019 ( Subtotal = $610,878 )
2019	2019	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	28	12/18/2018	COMPETING CONTINUATION	$610,878
2019	2018	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	27	5/14/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $610,878

Issue Date FY: 2018 ( Subtotal = $422,410 )
2018	2018	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	27	4/4/2018	NON-COMPETING CONTINUATION	$42,241
2018	2018	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	27	12/28/2017	NON-COMPETING CONTINUATION	$380,169
														Subtotal = $422,410

Issue Date FY: 2017 ( Subtotal = $422,410 )
2017	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	26	12/23/2016	NON-COMPETING CONTINUATION	$380,169
2017	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	26	5/24/2017	NON-COMPETING CONTINUATION	$42,241
														Subtotal = $422,410

Issue Date FY: 2016 ( Subtotal = $422,410 )
2016	2016	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	25	12/22/2015	NON-COMPETING CONTINUATION	$380,169
2016	2016	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	25	1/11/2016	NON-COMPETING CONTINUATION	$42,241
														Subtotal = $422,410

Issue Date FY: 2015 ( Subtotal = $431,864 )
2015	2015	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	24	12/19/2014	NON-COMPETING CONTINUATION	$392,603
2015	2015	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	24	1/13/2015	NON-COMPETING CONTINUATION	$39,261
														Subtotal = $431,864

Issue Date FY: 2014 ( Subtotal = $450,460 )
2014	2014	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	23	12/10/2013	COMPETING CONTINUATION	$450,460
														Subtotal = $450,460

Issue Date FY: 2013 ( Subtotal = $287,288 )
2013	2013	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	22	5/14/2013	NON-COMPETING CONTINUATION	$15,119
2013	2013	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	22	12/10/2012	NON-COMPETING CONTINUATION	$272,169
														Subtotal = $287,288

Issue Date FY: 2012 ( Subtotal = $302,410 )
2012	2012	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	21	1/25/2012	NON-COMPETING CONTINUATION	$30,241
2012	2012	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	21	12/8/2011	NON-COMPETING CONTINUATION	$272,169
														Subtotal = $302,410

Issue Date FY: 2011 ( Subtotal = $302,410 )
2011	2011	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	20	1/4/2011	NON-COMPETING CONTINUATION	$281,167
2011	2011	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	001	20	5/27/2011	NON-COMPETING CONTINUATION	$21,243
														Subtotal = $302,410

Issue Date FY: 2010 ( Subtotal = $312,407 )
2010	2010	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	19	12/30/2009	NON-COMPETING CONTINUATION	$312,407
														Subtotal = $312,407

Issue Date FY: 2009 ( Subtotal = $464,195 )
2009	2009	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Trans-NIH Recovery Act Research Support	001	18	7/15/2009	SUPPLEMENT FOR EXPANSION	$148,632
2009	2009	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Research Related to Deafness and Communication Disorders	000	18	10/28/2008	COMPETING CONTINUATION	$315,563
														Subtotal = $464,195

Issue Date FY: 2008 ( Subtotal = $309,781 ) (Continued on the next page)
Grand Total All Awards = $10,680,213

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Intracellular Calcium in Hair Cells

Award Number: R01DC001362

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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