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Olfactory receptor-based sensors for biomedical applications

Award Number: R35GM124871
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: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Olfactory receptor-based sensors for biomedical applications - Project Summary/Abstract Olfactory receptors (ORs) are one of the largest family of chemical detecting cell-surface receptors in humans. ORs are expressed beyond the olfactory tissue, with 55 ORs highly expressed ectopically (exORs) in 18 different tissues, where they drive tissue-specific processes including sperm chemotaxis and muscle regeneration. The majority of exORs, however, have no known ligands; they are orphans, which limits the ability to understand their role in human health, including 1) elucidation of exOR downstream pathways in the endogenous tissue, 2) the identification of exOR endogenous ligands, and ultimately 3) an assessment of exORs as potential therapeutic targets. During the MIRA renewal period, the goal is to leverage the OR-based sensor technology to generate large sets of high-quality experimental exOR-ligand data to train machine learning models to predict ligands for the 36 currently orphaned exORs. Such an algorithm would vastly accelerate exOR deorphanization, and may prove to be general, enabling the deorphanization of all 302 orphan ORs. The long- term goal is to use the identified ligands that activate the exORs to tease out their role in human health, including identifying the endogenous exOR ligands in the tissues in which they are overexpressed, and determining the downstream processes in which they are involved. This understanding will enable an assessment of exORs as therapeutic targets, and open the door to new, first-in-class therapeutics. Olfactory receptors belong to the class of cell surface proteins called G-protein coupled receptors (GPCRs). Non-sensory GPCRs are involved in a myriad of biological process, from cell migration to immunity, making them important therapeutic targets. GPCRs signal combinatorially, with ~100s of GPCRs expressed in mammalian cells signaling via a total of 17 G-protein subtypes—resulting in extensive crosstalk between GPCR signaling pathways, often with important therapeutic implications. A gap in knowledge exists in understanding the extent of GPCR signaling pathway crosstalk and its effect on cellular processes and animal behavior. Dissecting GPCR signaling pathway crosstalk will enable 1) the identification of GPCR signaling pathways leading to therapeutically desired outcomes, vis a vis pathways leading to side effects, towards the development of more precise and safer therapeutics, and 2) a more nuanced understanding of GPCR signaling that will be crucial for the engineering of next-generation therapeutic cells. During the MIRA renewal period the goal is to develop a chemogenetic toolset to combinatorially activate/deactivate multiple (≥ 3) GPCR signaling pathways while leaving the rest of the cell intact in order to fully dissect the effects of GPCR signaling crosstalk and its biomedical implications. The long-term goal is to ultimately enable combinatorial control of up to 17 different GPCR signaling pathways, providing access to cellular phenotypes that may explain how combinatorial GPCR activation can be leveraged for the development of new therapies and the GPCR-based circuit architecture could inspire the development of next-generation sense and response therapeutic 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: 2025 ( Subtotal = $366,660 )
2025	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	001	8	4/17/2025	NON-COMPETING CONTINUATION	$366,660
2025	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	7	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $366,660

Issue Date FY: 2024 ( Subtotal = $534,901 )
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	002	7	8/5/2024	NON-COMPETING CONTINUATION	$36,750
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	003	7	8/27/2024	SUPPLEMENT FOR EXPANSION	$167,402
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	001	7	4/4/2024	NON-COMPETING CONTINUATION	$330,749
2024	2021	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	5	4/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $534,901

Issue Date FY: 2023 ( Subtotal = $368,315 )
2023	2023	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	002	6	5/17/2023	COMPETING CONTINUATION	$368,315
2023	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	000	5	5/16/2023	NON-COMPETING CONTINUATION	$0
2023	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	001	5	5/16/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $368,315

Issue Date FY: 2021 ( Subtotal = $421,891 )
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	000	5	8/13/2021	NON-COMPETING CONTINUATION	$349,329
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	002	5	9/1/2021	SUPPLEMENT FOR EXPANSION	$72,562
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	001	5	8/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $421,891

Issue Date FY: 2020 ( Subtotal = $354,225 )
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	4	8/17/2020	NON-COMPETING CONTINUATION	$354,225
														Subtotal = $354,225

Issue Date FY: 2019 ( Subtotal = $358,888 )
2019	2019	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	3	8/20/2019	NON-COMPETING CONTINUATION	$358,888
														Subtotal = $358,888

Issue Date FY: 2018 ( Subtotal = $444,645 )
2018	2018	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	001	2	9/3/2018	SUPPLEMENT FOR EXPANSION	$82,677
2018	2018	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	2	8/30/2018	NON-COMPETING CONTINUATION	$361,968
														Subtotal = $444,645

Issue Date FY: 2017 ( Subtotal = $363,517 )
2017	2017	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	1	8/10/2017	NEW	$363,517
														Subtotal = $363,517

Grand Total All Awards = $3,213,042

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Olfactory receptor-based sensors for biomedical applications

Award Number: R35GM124871

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: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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