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Structural Biology Of G Protein-Coupled Receptors

Award Number: R35GM127086
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2018
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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Structural Biology Of G Protein-Coupled Receptors - Project Summary G protein-coupled receptors (GPCRs) constitute the largest membrane protein superfamily in the human genome, with over 800 unique sequences. GPCR-mediated signaling pathways play a key role in all physiological systems as well as many pathophysiological conditions and therefore represent important drug targets. GPCRs have a seven-transmembrane-helix (7TM) topology and contain multiple binding sites for orthosteric ligands and allosteric modulators. Upon recognition of their native ligands receptors transmit signal across the cell membrane to intracellular partner proteins, such as G proteins or β-arrestins. Developing a detailed understanding of functional mechanisms of GPCRs and facilitating design of novel drugs with high selectivity and potency require access to high-resolution three-dimensional structures, determination of which, however, remains a challenging task. We propose here a comprehensive research program which combines technology development with integrated structure-function studies focused on GPCR superfamily. The proposed research directions are designed to accelerate high-resolution structure determination of membrane proteins, improve our understanding of GPCR superfamily and answer specific questions on ligand specificity and selectivity as well as molecular mechanisms of action using several specific receptors as targets. Our approach integrate structural information on new receptors and complexes with data obtained from biophysical, biochemical and functional experiments through computer-based analysis and modeling. The long-term goal of our laboratory is to develop a deeper understanding of the molecular mechanisms of action of GPCR using the tools of structural biology and to apply the achieved insights towards the design and development of novel and efficacious therapeutics.


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 = $464,800 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	4/2/2026	NON-COMPETING CONTINUATION	$464,800
														Subtotal = $464,800

Issue Date FY: 2025 ( Subtotal = $464,800 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Biomedical Research and Research Training	001	7	4/11/2025	NON-COMPETING CONTINUATION	$464,800
2025	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Biomedical Research and Research Training	000	6	11/21/2024	COMPETING CONTINUATION	$0
														Subtotal = $464,800

Issue Date FY: 2024 ( Subtotal = $695,857 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Biomedical Research and Research Training	002	6	8/28/2024	SUPPLEMENT FOR EXPANSION	$231,407
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Biomedical Research and Research Training	001	6	3/22/2024	COMPETING CONTINUATION	$464,450
2024	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	12/6/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $695,857

Issue Date FY: 2022 ( Subtotal = $412,500 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	5/16/2022	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2021 ( Subtotal = $412,500 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	4/22/2021	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2020 ( Subtotal = $412,500 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	4/15/2020	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2019 ( Subtotal = $412,500 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	5/2/2019	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2018 ( Subtotal = $291,501 )
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	4/30/2018	NEW	$291,501
														Subtotal = $291,501

Grand Total All Awards = $3,566,958

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Structural Biology Of G Protein-Coupled Receptors

Award Number: R35GM127086

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2018

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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