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Regulation of hair cell mechanotransduction by PIP2

Award Number: F31DC022480
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Regulation of hair cell mechanotransduction by PIP2 - PROJECT SUMMARY Within the stereocilia of hair cells of the inner ear, a variety of molecules including proteins and lipids assemble into a mechanotransduction (MET) complex. This complex converts mechanical stimuli from sound waves into electrical signals that can then be propagated through the auditory pathway. Although many protein elements of the MET complex have been discovered, the lipid elements of this complex are poorly defined. Here, I propose to elucidate the molecular function of PIP2 in hair cell mechanotransduction. PIP2 has been shown to bind to TMIE, an essential subunit of the MET complex of cochlear hair cells that binds to TMC1, the likely pore-forming subunit of the MET channel. In addition, pharmacological depletion of PIP2 in hair cells decreases MET suggesting that the binding of PIP2 to TMIE affects MET channel function. To test this model and to define the mechanisms by which PIP2 affects MET in cochlear hair cells, I propose to combine biochemistry and electrophysiology in order to elucidate how TMIE mutations that perturb PIP2 binding affect MET. I anticipate that my studies will provide insights into the molecular mechanisms by which a phospholipid that is implicated in the regulation of the function of many ion channels contributes to the regulation of the mechanotransduction process in hair cells.


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: 2026 ( Subtotal = $49,538 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Research Related to Deafness and Communication Disorders	000	2	12/11/2025	NON-COMPETING CONTINUATION	$49,538
														Subtotal = $49,538

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Research Related to Deafness and Communication Disorders	001	1	8/7/2024	NEW	$0
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Research Related to Deafness and Communication Disorders	000	1	8/7/2024	NEW	$48,974
														Subtotal = $48,974

Grand Total All Awards = $98,512

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Regulation of hair cell mechanotransduction by PIP2

Award Number: F31DC022480

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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