Caenorhabditis elegans chemosensory bioassay for seven transmembrane receptor ligands

Abstract

This invention relates to methods for producing a transgenic C. elegans that expresses a human 7TMR pan-neuronally, such that said transgenic C. elegans exhibits a known phenotype. These transgenic C. elegans can be used in a variety of ways, including, but not limited to: (1) screening and identifying substances that bind to and activate particular human 7TMRs; (2) screening for substances that antagonize human 7TMR activation; (3) identifying human 7TMRs that may respond to particular substances; and (4) evaluating the specificity and efficacy of substances on human 7TMR activation.

1 - 13 . (Cancelled)  
     
     
         14 . A method for identifying at least one substance that agonizes the activity of a human 7-transmembrane receptor (h7TMR), said method comprising the steps of: 
 (a) providing at least one transgenic  C. elegans  whose genome comprises a nucleotide sequence encoding a human 7TMR, wherein said h7TMR is expressed in sensory neurons of said transgenic  C. elegans , wherein said sensory neurons do not correlate with behaviour, and wherein said at least one transgenic  C. elegans  does not exhibit a known phenotype because said human 7TMR is not activated by an endogenous ligand;    (b) contacting said at least one transgenic  C. elegans  with at least one test substance, wherein said at least one test substance is distributed in a medium;    (c) determining whether said at least one test substance causes said at least one said transgenic  C elegans  to exhibit a known phenotype; and    (d) identifying said at least one test substance that causes said at least one said transgenic  C elegans  to exhibit a known phenotype as an agonist of said human 7TMR.    
     
     
         15 . The method as claimed in  claim 14 , wherein the medium is chosen from the group of: buffer, growth medium, and agar.  
     
     
         16 . The method as claimed in  claim 14 , wherein the medium is a growth medium that comprises a biomolecular separation in a matrix.  
     
     
         17 . The methods as claimed in  claim 14 , wherein said matrix is chosen from the group of: agarose and polyacrylamide.