Mount Sinai School of Medicine

Linguagen Corp.

Hoffmann-la Roche Inc.

University of Washington

Robert F Margolskee

Liquan Huang

Minqing Rong

Marianna Max

Cristian A Perez

Ding Ming

Joseph A Beavo

Sami Damak

Y Gopi Shanker

The present invention relates to the discovery, identification and characterization of a transient receptor potential channel, referred to herein as TRP8, which is expressed in taste receptor cells and associated with the perception of bitter and sweet taste. The invention encompasses TRP8 nucleotides, host cell expression systems, TRP8 proteins, fusion proteins, polypeptides and peptides, antibodies to the TRP8 protein, transgenic animals that express a TRP8 transgene, and recombinant 'knock-out' animals that do not express TRP8. The invention further relates to methods for identifying modulators of the TRP8-mediated taste response and the use of such modulators to either inhibit or promote the perception of bitterness or sweetness. The modulators of TRP8 activity may be used as flavor enhancers in foods, beverages and pharmaceuticals.

TRP8, a transient receptor potential channel expressed in taste receptor cells

The present invention relates to the discovery, identification and characterization of a receptor protein, referred to herein as T1R3, which is expressed in taste receptor cells and associated with the perception of bitter and sweet taste. The invention encompasses transgenic animals and cells that do not express functional T1R3 protein, particularly knock-out animals and cells, and transgenic animals and cells that express a non-native T1R3 protein. Experimental model systems based on these animals and cells can be used to study T1R3-mediated taste transduction and responses of the components of the T1R3 signal transduction pathway to various tastants, furthering our understanding of the molecular biology and biochemistry of taste. Such model systems would also be useful for screening for novel tastants and taste modulators, such as enhancers of desirable flavors, and blockers of undesirable flavors.

T1R3 transgenic animals, cells and related methods

The present invention relates to methods for identifying inhibitors of the bitter taste response, and by methods of using such inhibitors to either block the perception of bitterness and/or promote the perception of a sweet taste. The inhibitors of the invention may be used as flavor enhancers in foods and pharmaceuticals. The methods of the invention may further be used to characterize the gustatory perception of novel tastants.

Inhibitors of the bitter taste response

Method of identifying bitter compounds by employing TRP8, a transient receptor potential channel expressed in taste receptor cells

Gustducin is a taste receptor cell heterotrimeric guanine nucleotide binding protein. Disclosed herein is the amino acid sequence of the gamma (&#x3b3;) subunit of gustducin, as well as polynucleotide sequences encoding the &#x3b3; subunit. Also disclosed are methods of modifying taste involving agents that inhibit or activate the gustducin &#x3b3; subunit, methods for identifying such taste modifying agents and various taste modifying agents.

Gustducin &#x3b3; subunit materials and methods

The present invention relates to novel methods of signal transduction in cells. In particular, the invention relates to signal transduction via a class of enzymes known as phosphodiesterase enzymes or PDEs. The invention also relates to a class of signaling molecules known as G-coupled protein receptors (GCPRs) and G-proteins. The invention provides novel methods to screen for and identify G-proteins and other compounds which modulate signaling by these two classes of proteins. In particular, the relates to novel assays which identify compounds that modulate (e.g., enhance or inhibit) binding between a PDE polypeptide and an effector activation domain of a G-protein.

Screening methods to identify compounds that modulate type I phosphodiesterase (PDE) activity

A novel taste cell specific guanine nucleotide binding protein, gustducin, is disclosed as well as polynucleotide sequences encoding the .alpha. subunit of gustducin. Also disclosed are methods of modifying taste involving agents that inhibit or activate the gustducin .alpha. subunit, methods for identifying such taste modifying agents and various taste modifying agents.

Gustducin materials and methods

Gustducin polypeptides and fragments

Gustducin polynucleotides, vectors, host cells and recombinant methods

Asymmetrically tailed plasmid primers are provided, each of which comprises a cut, double-stranded DNA plasmid containing a functional origin of replication, at least one functional selection marker gene, a 3' oligo (dT) tail and a 3' oligo (dC) or oligo (dG) tail which is terminated by a phosphate group. Methods for making and using the primers for the highly efficient production of complex cloning libraries and a kit for carrying out the cloning method of the invention are also provided.

Growing community of inventors

Upper Montclair, NJ, United States of America

Robert F Margolskee