Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

A robust assay for detecting agonist bias in living cells.

Award Number: R44GM125390
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: 08/21/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2022

Group Awards By:

View Award Description

A robust assay for detecting agonist bias in living cells. - ! Project Summary The objective of this SBIR Phase II project is to optimize and validate a prototype assay for ligand bias to be used in screening drugs that target seven transmembrane G- protein coupled receptors (GPCRs). The assay is based on genetically-encoded fluorescent biosensors that report signaling with a change in fluorescence intensity. Aim 1 of this project involves engineering and testing to increase the change in fluorescence intensity of biosensors for β arrestin1 and β arrestin2. This involves using an established workflow and screening process to iteratively improve linkers in between a very bright green fluorescent protein and β-arrestin. This proprietary process consists of randomly mutagenizing key amino acids to create low diversity libraries of candidate biosensors that are screened for improved fluorescence properties. Aim 2 involves optimizing assay parameters and validating the multiplex assay comprised of the optimized green fluorescent biosensor for β arrestin, co-expressed with existing red fluorescent biosensors for diacylglycerol (DAG) or cyclic AMP. The red sensor indicates G-protein mediated activity while the green sensor indicates arrestin activity. The assay will be validated with a select panel of GPCRs and small molecule and peptide agonists. GPCRs, are one of the largest family of drug targets. Their activity is mediated by both G proteins and β-arrestins which activate a network of distinct signaling pathways. Depending upon the GPCR and cell type, biased agonism can be therapeutically beneficial or produce unwanted or harmful side effects (Violin and Lefkowitz, 2007). Quantifying bias in GPCR signaling could help to identify new therapeutic drugs that avoid adverse effects. Detecting agonist bias early in the screening process, in cell types that are relevant to disease, has the potential to reduce the risk and cost of drug discovery.


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: 2023 ( Subtotal = $0 )
2023	2020	MONTANA MOLECULAR LLC	366 GALLATIN PARK DR	BOZEMAN	MT	59715	GALLATIN	USA	Biomedical Research and Research Training	000	3	4/28/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	MONTANA MOLECULAR LLC	366 GALLATIN PARK DR STE A	BOZEMAN	MT	59715	GALLATIN	USA	Biomedical Research and Research Training	000	3	2/11/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $600,181 )
2020	2020	MONTANA MOLECULAR LLC	366 GALLATIN PARK DR STE A	BOZEMAN	MT	59715	GALLATIN	USA	Biomedical Research and Research Training	000	3	6/24/2020	NON-COMPETING CONTINUATION	$600,181
														Subtotal = $600,181

Issue Date FY: 2019 ( Subtotal = $634,836 )
2019	2019	MONTANA MOLECULAR LLC	366 GALLATIN PARK DR STE A	BOZEMAN	MT	59715	GALLATIN	USA	Biomedical Research and Research Training	000	2	6/25/2019	COMPETING CONTINUATION	$634,836
														Subtotal = $634,836

Grand Total All Awards = $1,235,017

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A robust assay for detecting agonist bias in living cells.

Award Number: R44GM125390

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: 08/21/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2022

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer