Friday, August 29, 2025 8/29/2025

Optical Tools to Study Purinergic Signaling

Award Number: R01GM134380
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: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Optical Tools to Study Purinergic Signaling - Project Summary/Abstract Extracellular ATP and ADP are mediators of purinergic signaling in cell-to-cell communication in virtually every tissue. Autocrine and paracrine purinergic signaling contributes to normal cellular functions such as immune cell chemotaxis and cell volume regulation, and purinergic signaling also contributes to pathology in injury, infection, sepsis, and a number of diseases. Notably, extracellular ATP and ADP mediate purinergic signaling between cells with both short-term and long-term effects. However, it has been a challenge to study the cellular and molecular mechanisms by which ATP and ADP control distinct signaling events because their levels are spatially heterogeneous and purinergic signaling can vary significantly from cell-to-cell. Clearly, direct measurements of extracellular nucleotides are needed, but current methods are not well adapted to measuring fluctuations in the low extracellular nucleotide concentrations expected in live specimens. To overcome this barrier, we will use protein engineering to develop high affinity cell-surface sensors that can be used to resolve the complex spatial and temporal dynamics of ATP and ADP release, clearance, and purinergic receptor activation. To demonstrate the application of our sensors and also guide their optimization, we will study neuron-glia purinergic signaling in the brain. In particular, we will use our sensors to learn how metabolic state affects the function of microglia, the resident immune cells in the brain, in regulating the regional purinergic dynamics that impact local neuronal activity. The proposed series of multiplexed imaging studies that pair our purinergic sensors with sensors of downstream signaling should directly visualize core elements of neuron-glia purinergic communication in an integrated manner. This should provide valuable insight into novel mechanisms responsible for the coupling between brain energy metabolism and excitability. Furthermore, the genetically-encoded tools developed through this proposal should be broadly applicable to deeper study of any purinergic system.


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 = $355,707 )
2025	2025	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY HILLS	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	001	4	8/12/2025	NON-COMPETING CONTINUATION	$35,570
2025	2025	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY HILLS	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	000	4	12/20/2024	NON-COMPETING CONTINUATION	$320,137
														Subtotal = $355,707

Issue Date FY: 2024 ( Subtotal = $353,168 )
2024	2024	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY HILLS	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	000	3	1/3/2024	NON-COMPETING CONTINUATION	$317,851
2024	2024	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY HILLS	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	001	3	6/17/2024	NON-COMPETING CONTINUATION	$35,317
														Subtotal = $353,168

Issue Date FY: 2023 ( Subtotal = $442,176 )
2023	2023	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY HILLS	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	002	2	2/21/2023	SUPPLEMENT FOR EXPANSION	$90,194
2023	2023	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY HILLS	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	001	2	2/15/2023	NON-COMPETING CONTINUATION	$35,198
2023	2023	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY HILLS	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	000	2	1/25/2023	NON-COMPETING CONTINUATION	$316,784
														Subtotal = $442,176

Issue Date FY: 2022 ( Subtotal = $701,711 )
2022	2022	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	004	1	9/2/2022	SUPPLEMENT FOR EXPANSION	$90,194
2022	2022	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	001	1	1/18/2022	NEW	$0
2022	2022	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	003	1	8/30/2022	SUPPLEMENT FOR EXPANSION	$241,000
2022	2022	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	002	1	5/26/2022	SUPPLEMENT FOR EXPANSION	$14,806
2022	2022	WELLESLEY COLLEGE	106 CENTRAL ST	WELLESLEY	MA	02481	NORFOLK	USA	Biomedical Research and Research Training	000	1	12/28/2021	NEW	$355,711
														Subtotal = $701,711

Grand Total All Awards = $1,852,762

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Optical Tools to Study Purinergic Signaling

Award Number: R01GM134380

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: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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