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 Virion-Display Oscillator Array and Detection Platform for Quantification of Transmembrane Protein Binding Kinetics

Award Number: R33CA235294
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 02/29/2024

Group Awards By:

View Award Description

A Virion-Display Oscillator Array and Detection Platform for Quantification of Transmembrane Protein Binding Kinetics - ABSTRACT Transmembrane proteins, such as G-protein-coupled receptors (GPCRs), are critical for many cellular functions. They are also the most popular drug targets for various diseases, including cancer. For both understanding cellular functions and drug development, it is necessary to measure their binding activities with molecular ligands and drug candidates. However, this has been a difficult task because of two challenges. First, transmembrane proteins are difficult to extract and purify, and they often lose their native conformations after isolation from the cellular membranes. Second, even if a membrane protein is successfully isolated, it remains challenging to measure its binding to ligands, especially with small molecule ligands. Small molecules comprise ~90% of the current drugs, but their binding kinetics cannot be easily measured with the existing detection technologies. This project addresses both challenges with a virion oscillator technology. Human GPCRs are displayed on the viral envelopes of human herpes simplex virus-1 (HSV-1), which removes the need of extraction, purification, and reconstitution of the transmembrane proteins. Each virion is then tethered to a sensor chip with a flexible polymer linker to form an oscillator. By applying an alternating electric field to the chip, the virion oscillates, and the oscillation amplitude is tracked in real-time with sub-nanometer precision using a plasmonic imaging technique. Upon binding of ligands or drugs to the GPCRs on the virion envelopes, the oscillation amplitude changes, from which binding kinetics and affinity are quantified. This project combines the virion display and microarray strengths at Johns Hopkins University, and plasmonic imaging and biosensing expertise at Arizona State University. The team has been working together and completed substantial preliminary experiments to demonstrate this new detection platform. The goal of this R33 project is to transform the technology into a powerful high-throughput platform for studying membrane proteins by 1) developing virion oscillator microarray chips (with 315 non-odorant human GPCRs on a single chip), 2) developing a plasmonic imaging system for high-throughput quantification of molecular binding kinetics, and 3) validating the virion oscillator microarray technology with cancer related GPCRs. It is anticipated that the virion oscillator detection technology will become a unique tool for studying cellular functions of membrane proteins, and quantifying binding of large and small molecule drugs with any types of membrane proteins.


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	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Cancer Biology Research	000	3	6/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $362,612 )
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Biology Research	000	3	2/23/2022	NON-COMPETING CONTINUATION	$333,010
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Biology Research	001	3	5/9/2022	NON-COMPETING CONTINUATION	$29,602
														Subtotal = $362,612

Issue Date FY: 2021 ( Subtotal = $377,383 )
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Biology Research	000	2	2/19/2021	NON-COMPETING CONTINUATION	$377,383
														Subtotal = $377,383

Issue Date FY: 2020 ( Subtotal = $391,113 )
2020	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Biology Research	001	1	6/29/2020	NEW	$0
2020	2020	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Biology Research	000	1	2/27/2020	NEW	$391,113
														Subtotal = $391,113

Grand Total All Awards = $1,131,108

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A Virion-Display Oscillator Array and Detection Platform for Quantification of Transmembrane Protein Binding Kinetics

Award Number: R33CA235294

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 02/29/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer