The project outlined in this application will focus on the molecular mechanism underlying mammalian odor perception through the investigations of specific anosmia and sensitization of androstenone and other ligands. Androstenone odorant receptor(s) will be identified using a screening system matching receptors to their cognate ligands. Such system will be strengthened by a structure-function analysis of the receptor- transporting proteins (RTPs). Deletion and chimeric series of RTPs will be assessed in cell-surface immunostaining and luciferase assay to identify key regions. Domains of interaction between RTPs and odorant receptors will be investigated using the split-ubiquitin yeast two-hybrid system. The polymorphisms in candidate androstenone odorant receptor(s) will be evaluated for correlation with the anosmic phenotype by genotyping a psychophysically-analyzed population. Mouse models of androstenone-anosmic and osmic strains will be used for similar SNP genotype analysis, as well as mRNA and protein expression analyses. In vivo sensitization and experiments in heterologous cell will shed lights how ligand exposure facilitates androstenone sensitization. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DC008480-02
Application #
7249411
Study Section
Special Emphasis Panel (ZRG1-DIG-H (29))
Program Officer
Cyr, Janet
Project Start
2006-07-01
Project End
2007-12-31
Budget Start
2007-07-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2007
Total Cost
$15,842
Indirect Cost
Name
Duke University
Department
Genetics
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Saito, Harumi; Chi, Qiuyi; Zhuang, Hanyi et al. (2009) Odor coding by a Mammalian receptor repertoire. Sci Signal 2:ra9
Zhuang, Hanyi; Matsunami, Hiroaki (2007) Synergism of accessory factors in functional expression of mammalian odorant receptors. J Biol Chem 282:15284-93