A G-Protein Receptor Based Biosensor for Detection and Identification of Chemicals

Web Published:
12/1/2011
Description:

Princeton Invention # 05-2225

 

           

Researchers at Princeton University have developed a robust system for functional expression of heterologous G-protein coupled receptors (GPCRs) in the yeast Saccharomyces cerevisiae and have successfully applied this system to develop novel biosensors based on the concepts of combinatorial recognition.  Their work has demonstrated the feasibility of modifying existing GPCR¿s to constitute an array of sensors that in sum have recognition far in excess of the number of detector elements.  Sensors based on GPCRs organized in a combinatorial array can provide a uniform detector design that could  (1) detect at very low concentrations  tens to hundreds of thousands of analytes, (2)  recognize any of a very large collection of known analytes, (3) detect and distinguish the presence of any new, previously unknown , analyte and add the new analyte to its repertoire of known analytes, (4) perform detection in the background of other, confounding analytes and (5) provide information on sources of analytes.  This invention can be used immediately in the specialty chemicals/pharmaceutical manufacturing industries.

 

The invention also holds the potential to be further developed for use in integrated devices for monitoring chemical environments. Possible applications include air and groundwater monitoring, biohazard detection, drug testing and instantaneous blood chemistry monitoring. This later tool could be quite valuable in the pharmaceutical industry for evaluating drug metabolism during discovery research and in pharmacogenomic studies in late stage development.

 

Biological assays are frequently utilized for chemical detection because of their convenience, as well as their high degree of sensitivity and specificity relative to alternative means of chemical analysis.  Presently the vast majority of biological assays for chemical analytes are based on monoclonal antibodies or coupled enzyme assays. The region of chemical space immediately addressable by the invention includes all GPCR ligands, which encompass nearly 40% of drug compounds currently on the market, and chemically related compounds, which would likely include the synthetic precursors of many drug compounds. The invention relies on repeated mutagenesis and selection of receptors to increase the breadth of the chemical repertoire recognizable by GPCRs and to create ensembles of receptors capable of discriminating among related chemicals that could not be distinguished by a single naturally occurring receptor. The ease of mutagenesis and selection for this chemical analysis is far greater than for coupled enzyme assays, and the ensemble of chemicals that can be analyzed by GPCRs encompasses an economically relevant set of compounds, many of which are not readily addressable by alternative techniques.

 

This system also is distinct from alternative chemical detection technologies in that the GPCRs used for chemical analysis are linked to cellular signal transduction pathways in a variety of eukaryotic cells. This affords the opportunity to design genetically selectable chemical screens, in which the chemical analyte of interest is capable of controlling the life or death, or other properties of a cell. Currently, neither enzymatic assays nor antibody-based chemical assays can be effectively linked to cellular signaling pathways in a systemic way.

 

  

 

References :

 

Creation of GPCR-based chemical sensors by directed evolution in yeast, Protein Engineering, Design & Selection, Vol 10, No.1, pp.1-8, 2006

 

 

Princeton is currently seeking industrial collaborators to further the development and commercialization of this technology. Patent protection is pending.

 

 

For more information on Princeton University Invention # 05-2225 please contact:

           

 

                        Laurie Tzodikov

                        Office of Technology Licensing and Intellectual Property

                        Princeton University

                        4 New South Building

                        Princeton, NJ 08544-0036

                        (609) 258-7256

                        (609) 258-1159 fax

                        tzodikov@princeton.edu

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
tzodikov@Princeton.EDU
Inventors:
James Broach
Addison Ault
Keywords: