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Exploring the Biophysical Landscape of Tip Density Biomolecular Condensates in Mechanosensory Stereocilia

Award Number: F31DC021881
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: 01/05/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Exploring the Biophysical Landscape of Tip Density Biomolecular Condensates in Mechanosensory Stereocilia - PROJECT SUMMARY The development and function of hair cell stereocilia in the cochlea are essential for our sense of hearing, as they play a pivotal role in detecting sound through their mechanosensory capabilities. Stereocilia, organized into rows of graded height on the hair cell surface, are susceptible to damage caused by loud sounds and the aging process, leading to irreversible hearing loss. The architecture of stereocilia is critical for detecting sound and is regulated by a structural protein called actin that forms a rigid scaffold of filaments within these structures. My overarching goal is to understand the regulatory mechanisms that govern actin filament growth and ensure the correct development of stereocilia. In this proposal, I explore the function of the molecular motor protein myosin 15 (MYO15A) that controls actin filament assembly and stereocilia size. Mutations in MYO15A cause human hereditary hearing loss, DFNB3, underlying the essential activity of this protein in the cochlea. The central focus of my proposal is to discover how MYO15A and its associated proteins, known as the 'elongation complex' (EC), can control actin polymerization and stimulate stereocilia growth. My preliminary data along with the published work of others, have revealed a unique ability of MYO15A and EC proteins to form biomolecular condensate that are hypothesized to form the stereocilia tip density that controls actin filament elongation. The properties of these MYO15A-EC condensates are poorly understood, but highly relevant to stereocilia biology. In this proposal, I will conduct a comprehensive characterization of the biophysical properties of MYO15A-EC tip density condensates and explore their potential as reaction compartments optimized for actin filament growth. In Aim 1, I will measure the material properties and microrheology of purified MYO15A-EC tip density condensates, revealing their structural makeup. In Aim 2, I will test the hypothesis that MYO15A-EC tip-density condensates can potentiate actin filament growth. This work will utilize cutting-edge experimental approaches including optical trapping force spectroscopy and single-molecule microscopy techniques. The results from these experiments will reveal the fundamental properties of MYO15A-EC tip density condensates and advance our understanding of how stereocilia are built and maintained. Completion of this project will advance my long-term goal of manipulating stereocilia biology therapeutically to treat hearing loss in patients.


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: 2027 ( Subtotal = -$403 )
2027	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	000	2	10/27/2026	NON-COMPETING CONTINUATION	-$403
														Subtotal = -$403

Issue Date FY: 2025 ( Subtotal = $43,946 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	001	2	6/3/2025	NON-COMPETING CONTINUATION	$564
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	000	2	12/9/2024	NON-COMPETING CONTINUATION	$43,382
														Subtotal = $43,946

Issue Date FY: 2024 ( Subtotal = $43,382 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	002	1	4/24/2024	NEW	$1,280
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	000	1	12/16/2023	NEW	$42,102
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Research Related to Deafness and Communication Disorders	001	1	12/16/2023	NEW	$0
														Subtotal = $43,382

Grand Total All Awards = $86,925

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Exploring the Biophysical Landscape of Tip Density Biomolecular Condensates in Mechanosensory Stereocilia

Award Number: F31DC021881

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: 01/05/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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