Abstract
| Grant Number: | 5R43GM072379-02 |
| Project Title: | Detection of GPCR Function in Cell-free Nanoscale System |
Abstract: DESCRIPTION (provided by applicant):
The G protein-coupled receptor (GPCR) CXCR4 is a determinant of the pathogenesis of HIV-1 infection and breast cancer, but efforts to develop drugs that modify its function have been unsuccessful. Traditional assays that screen GPCR function mostly use live cells or cell membrane fragments, formats that are limited by poor receptor purity, stringent environmental requirements, unacceptable variability, and an inability to be miniaturized, prohibiting their application to more versatile micro- and nano-scale detection technologies. Furthermore, traditional assays for GPCR activation often involve detection of downstream signaling events such as calcium release which are not stimulated by a number of important GPCRs and G proteins. A nanometer-scale, cell-free assay for GPCR activation that can be applied to microfluidic drug-screening devices could have a major impact on the discovery of drugs to difficult GPCR targets, and this proposal is designed to produce such a system. Our approach has three major advantages compared with existing assays: 1) simplicity, 2) the ability to be miniaturized to the nanometer scale, and 3) the ability to detect diverse and difficult GPCRs that conventional systems fail to detect. The product will facilitate high throughput screening of GPCRs, orphan ligand-receptor pairing, and the development of therapeutics that treat AIDS and breast cancer.
Thesaurus Terms:
bioassay, biosensor device, cell component structure /function, cell free system, cell surface receptor, method development, nanotechnology, protein structure function, sensory signal detection
drug detection, microarray technology, protein protein interaction, receptor binding, receptor expression
bioengineering /biomedical engineering, biotechnology, fluorescence resonance energy transfer, high throughput technology
| Institution: | INTEGRAL MOLECULAR |
| 3701 MARKET ST, STE 340 |
| PHILADELPHIA, PA 191045502 |
| Fiscal Year: | 2006 |
| Department: | |
| Project Start: | 01-SEP-2005 |
| Project End: | 28-FEB-2008 |
| ICD: | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
| IRG: | ZRG1 |
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