Monday, June 23, 2025 6/23/2025

A phenotypic screen for compounds that differentially affect excitatory and inhibitory neuronal signaling

Award Number: R44MH121169
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/08/2019
PERIOD OF PERFORMANCE END DATE: 10/31/2024

Group Awards By:

View Award Description

A phenotypic screen for compounds that differentially affect excitatory and inhibitory neuronal signaling - Project Summary: Maintaining the appropriate balance of excitation (E) vs. inhibition (I) in the nervous system is essential for normal brain function, as disruptions in E/I balance are associated with disorders such as autism spectrum disorder (ASD), schizophrenia, and seizures. Development of therapeutics for ASD and schizophrenia has lagged due to their multifactorial etiology and challenges in modeling relevant biology in scalable in vitro assays. The Optopatch platform recently developed at Q-State Biosciences, which uses engineered optogenetic proteins, custom microscopes, and software, makes it possible to simultaneously stimulate (blue light) and record (red light) electrical activity from ~100 neurons with 1 millisecond temporal resolution, single-cell spatial resolution and high signal-to-noise ratio. In addition to measurements of intrinsic excitability, patterned blue light can be used to probe synaptic connections by stimulating a subset of neurons and recording postsynaptic potentials (PSPs) in all remaining cells. The Optopatch assays, which record signals in individual neurons, can be paired with fluorescent labels of inhibitory neurons to identify compounds that differentially affect signaling in excitatory and inhibitory cells and would be expected to shift the E/I balance. In Phase I of this project, we propose to 1) adapt the established Q-State assays for intrinsic excitability and synaptic transmission to measure the E/I balance and 2) validate these assays using tool compounds and gene knockdowns expected to shift the E/I balance. In Phase II, we propose to 3) screen annotated compound libraries, 4) confirm that proteins targeted by compounds in the library can modulate the E/I balance, and 5) validate that identified targets can also shift the E/I balance in human stem-cell derived neurons and in rodent brain slice. The identified protein targets will serve as a starting point for drug discovery, and identified FDA- approved compounds may be repurposed for new indications. The suite of tools developed here will pave a new path for developing E/I-modulating therapeutics for treating complex neurological disorders such as autism and schizophrenia.


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 = $0 )
2025	2023	QUIVER BIOSCIENCE INC.	150 CAMBRIDGEPARK DRIVE 5TH FLOOR	CAMBRIDGE	MA	02140	MIDDLESEX	USA	Mental Health Research Grants	000	3	3/25/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	QUELLTX INC	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	003	3	2/16/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	QUELLTX INC	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	004	3	8/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	QUELLTX INC	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	002	3	1/8/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$404,281
2024	2022	Q-STATE BIOSCIENCES	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	2	11/23/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
2024	2022	Q-STATE BIOSCIENCES, INC	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	001	2	1/8/2024	EXTENSION WITH OR WITHOUT FUNDS	-$404,281
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $575,445 )
2023	2023	QUELLTX INC	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	003	3	7/27/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$635,498
2023	2022	Q-STATE BIOSCIENCES	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	001	2	1/17/2023	EXTENSION WITH OR WITHOUT FUNDS	-$49,429
2023	2022	Q-STATE BIOSCIENCES	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	002	2	7/12/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
2023	2019	Q-STATE BIOSCIENCES	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	1	1/17/2023	NEW	-$10,624
														Subtotal = $575,445

Issue Date FY: 2022 ( Subtotal = $995,203 )
2022	2022	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	2	7/29/2022	EXTENSION WITH OR WITHOUT FUNDS	$995,203
2022	2022	Q-STATE BIOSCIENCES	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	002	2	8/11/2022	EXTENSION WITH OR WITHOUT FUNDS	$60,053
2022	2019	Q-STATE BIOSCIENCES	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	001	1	8/11/2022	NEW	-$60,053
														Subtotal = $995,203

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	1	5/19/2021	NEW	$0
2021	2019	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	001	1	8/4/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	1	7/24/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $585,093 )
2019	2019	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Mental Health Research Grants	000	1	8/8/2019	NEW	$585,093
														Subtotal = $585,093

Grand Total All Awards = $2,155,741

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A phenotypic screen for compounds that differentially affect excitatory and inhibitory neuronal signaling

Award Number: R44MH121169

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/08/2019

PERIOD OF PERFORMANCE END DATE: 10/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer