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Identify cell surface protein ligand candidates for understudied adhesion GPCRs using a sensitive cell-based approach

Award Number: R03TR004206
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Identify cell surface protein ligand candidates for understudied adhesion GPCRs using a sensitive cell-based approach - PROJECT SUMMARY/ABSTRACT Adhesion G protein-coupled receptors (aGPCRs) are a group of 33 poorly characterized non-olfactory GPCRs with distinct features including autocatalytic processing and large extracellular regions. aGPCRs are involved in a myriad of biological processes and some of them are associated with diseases, especially a wide range of cancers. The extracellular regions of many of the aGPCRs contain domains that are known to be involved in protein-protein interactions, suggesting that binding to cell surface protein ligands may play an important role in their mechanisms of action. The majority of aGPCRs, however, are orphan receptors without known ligands. Identification of ligands for these aGPCRs should help understand their physiological functions and roles in cancer development. A major challenge for identifying ligands involved in ligand-receptor interactions at the cell-cell interface is that they tend to bind their receptors very weakly and currently available methods do not have enough sensitivity. To overcome this, we propose to employ a novel and highly sensitive cell-based approach to identify protein ligands for 17 understudied orphan aGPCRs. The feasibility of the approach has been tested using model ligands and receptors that are known bind to each other with low affinities. We will use the cell-based approach to screen a collection of transmembrane proteins to identify ligand candidates for the aGPCRs. Ligand candidates identified in this study will pave the way for more in-depth characterization of their bindings to respective aGPCRs and the functional consequences of the bindings in future studies.


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: 2024 ( Subtotal = $0 )
2024	2022	THE NEMOURS FOUNDATION	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Trans-NIH Research Support	000	1	5/22/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $142,000 )
2022	2022	NEMOURS FOUNDATION, THE	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Trans-NIH Research Support	000	1	5/19/2022	NEW	$142,000
														Subtotal = $142,000

Grand Total All Awards = $142,000

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Identify cell surface protein ligand candidates for understudied adhesion GPCRs using a sensitive cell-based approach

Award Number: R03TR004206

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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