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Structural dynamics of human odorant receptors in olfaction

Award Number: R01DC021585
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Structural dynamics of human odorant receptors in olfaction - PROJECT SUMMARY Our sense of smell depends on our ability to detect and discriminate a vast array of odor molecules. In vertebrates, odors are predominantly detected by odorant receptors (ORs), which are G protein-coupled receptors (GPCRs) in vertebrates. The human genome encodes ~400 ORs, providing our olfactory system with the ability to detect diverse odorants. Despite incredible advances in our understanding of GPCR function, the fundamental molecular logic of odorant recognition by ORs remains elusive. It is unclear why closely related ORs can have distinct odorant preferences, or why some ORs respond to a small subset of odorants while others are more broadly responsive. Moreover, the process by which an odorant turns an OR “on” is not well understood. Recently, our collaborative team determined the first experimental structure of a vertebrate OR, the human receptor OR51E2, which provided critical insights into molecular recognition and OR activation. Building on this advance, we will address three fundamental aspects of odorant receptor biology: 1) Identify OR features that are responsible for odorant selectivity, 2) Reveal distinctions in odorant recognition by Class I and Class II ORs, and 3) Describe the fundamental mechanisms for how odorants activate ORs. Towards this end, we will combine structure determination with iterative mutagenesis studies and molecular dynamics simulations, thereby providing direct insight into the molecular logic of odorant recognition and OR activation. The proposed studies will provide fundamental insights into the structure and dynamics of OR function and yield inroads into an atomic framework for understanding our sense of smell.


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 = $583,657 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Research Related to Deafness and Communication Disorders	000	3	12/2/2025	NON-COMPETING CONTINUATION	$583,657
														Subtotal = $583,657

Issue Date FY: 2025 ( Subtotal = $648,575 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Research Related to Deafness and Communication Disorders	001	2	4/26/2025	NON-COMPETING CONTINUATION	$64,857
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Research Related to Deafness and Communication Disorders	000	2	11/27/2024	NON-COMPETING CONTINUATION	$583,718
														Subtotal = $648,575

Issue Date FY: 2024 ( Subtotal = $679,394 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Research Related to Deafness and Communication Disorders	000	1	10/19/2023	NEW	$679,394
														Subtotal = $679,394

Grand Total All Awards = $1,911,626

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Structural dynamics of human odorant receptors in olfaction

Award Number: R01DC021585

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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