The umami taste of amino acids (especially glutamate) and sweetness are the two appetitive taste qualities that are critical for our healthy attraction to protein and carbohydrate (energy) macronutrients. The likely evolutionary pressure for an appetitive protein taste system is our nutritional need: access to sources of dietary protein is essential for survival and kwashiorkor (dietary protein deficiency) is one of the leading causes of death in children in developing countries. Despite its importance in dietary selection, human umami taste remains one of the most poorly understood of the five taste qualities and its genetic and molecular determinants remain largely unknown. Three classes of glutamate receptors found within taste receptor cells have been associated with cell signaling in response to amino acids and ribonucleotides: (i) TAS1Rs, (ii) metabotropic-GluRs, and (iii) ionotropic-NMDA receptors. However, their respective roles in human umami taste perception are not known. The long term goal of the proposed work is to elucidate genetic and molecular mechanisms that are responsible for the human sensation of `umami'taste. The objectives of the proposed project are to clarify the roles of these three receptor classes, to identify other genes that may be involved with human umami taste perception, and to functionally test variant receptors associated with umami phenotypes.
The specific Aims of this Proposal are: I. Identify variant genes and/or genome-wide loci associated with umami blindness. II. Characterize any umami perceptual phenotypes related to glutamate receptor SNPs. III. Define variant glutamate receptor stimulus-response functions in expression assays.PROJECT NARRATIVE This proposal will contribute to human health by identifying genes associated with human protein/amino acid taste (umami), which will subsequently guide nutritional intervention in protein malnourished people. Taste is significantly linked to nutrition, since our decision to accept or reject foods is ultimately based on our evaluation of food tastes. Hence, people who lose their sense of taste, such as radiotherapy patients, suffer nutrionally. Frequently, children in developing nations prefer foods with high levels of sugar, when available, over other food types. Too little protein in the diet (Kwashiorkor) is associated with one in every two children's deaths in the developing world. Since children with protein malnutrition prefer foods that have added free amino acids in experimental settings, a better understanding of amino acid taste mechanisms could guide the engineering of more appetitive foods that could help alleviate their malnutrition. Despite its importance in dietary selection, human umami taste remains one of the most poorly understood of the five taste qualities and its genetic and molecular determinants remain largely unknown. We will characterize how genes of candidate umami taste receptors and other genetic loci affect perceptual attributes of human amino acid taste through interdisciplinary studies that combine human perception, genetics, and molecular receptor functions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002995-12
Application #
7535486
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Davis, Barry
Project Start
1996-12-01
Project End
2009-09-30
Budget Start
2008-12-01
Budget End
2009-09-30
Support Year
12
Fiscal Year
2009
Total Cost
$324,608
Indirect Cost
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Hwang, Liang-Dar; Gharahkhani, Puya; Breslin, Paul A S et al. (2018) Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste. BMC Genomics 19:678
Hwang, Liang-Dar; Zhu, Gu; Breslin, Paul A S et al. (2015) A common genetic influence on human intensity ratings of sugars and high-potency sweeteners. Twin Res Hum Genet 18:361-7
Campbell, Michael C; Ranciaro, Alessia; Zinshteyn, Daniel et al. (2014) Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa. J Hum Genet 59:349-52
Campbell, Michael C; Ranciaro, Alessia; Zinshteyn, Daniel et al. (2014) Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa. Mol Biol Evol 31:288-302
Platte, Petra; Herbert, Cornelia; Pauli, Paul et al. (2013) Oral perceptions of fat and taste stimuli are modulated by affect and mood induction. PLoS One 8:e65006
Breslin, Paul A S (2013) An evolutionary perspective on food and human taste. Curr Biol 23:R409-18
Coldwell, Susan E; Mennella, Julie A; Duffy, Valerie B et al. (2013) Gustation assessment using the NIH Toolbox. Neurology 80:S20-4
Wise, Paul M; Breslin, Paul A S (2013) Individual differences in sour and salt sensitivity: detection and quality recognition thresholds for citric acid and sodium chloride. Chem Senses 38:333-42
Wise, Paul M; Breslin, Paul A S; Dalton, Pamela (2012) Sweet taste and menthol increase cough reflex thresholds. Pulm Pharmacol Ther 25:236-41
des Gachons, Catherine Peyrot; Mura, Emi; Speziale, Camille et al. (2012) Opponency of astringent and fat sensations. Curr Biol 22:R829-30

Showing the most recent 10 out of 26 publications