We are interested in rational modulation of biological function and in facilitating innovative design of tastants, taste modulators and drugs.
Main focus is on bitter and sweet taste modalities. There are multiple bitter taste GPCR subtypes (called T2Rs), and the number is species-specific (3 in chicken, 25 in human).
To study this complexity, we have established and expanded the BitterDB database of bitter ligands. The database currently holds information on over 1000 bitter molecules, their associated receptors in various species, SNPs in the receptors and more. There are over 23,000 users of the BitterDB worldwide.
Based on this information, and by gathering information also on non-bitter molecules, we have developed a machine-learning classifier, which predicts from molecules chemical structure, whether it is likely to be bitter or non-bitter. This BitterPredict tool enabled to evaluate the abundance of bitter molecules in different datasets. Specifically, it is usually assumed that bitterness signals toxicity. We applied BitterPredict to datasets of toxic molecules and found that despite common assumption, toxicity does not strongly correlate with toxicity.
Another point of interest relates to molecular recognition: how is it possible for a single receptor to be activated by dissimilar ligands? We found that the chemophysical characteristics, subpockets, and ligand-dependent use of interactions of the orthosteric bindings site, provide the versatility needed for accomodating multiple ligands.
Interestingly, not only does a single T2R recognize multiple bitter ligands, but a single bitter molecule can activate several T2Rs. However, bitterants that activate multiple T2Rs are not more bitter (at least not more aversive for chicken) than T2R-specific ones.
Because of bitter taste aversiveness, we hypothesized that might affect behavior and emotions. A significant negative effect on mood was caused by exposure to bitter-tasting mouth-rinse. Somewhat suriprisingly, the effect was asymmetric: sweet-tasting mough rinse did not elevate mood.
Novel sweeteners and taste modifiers are currently under study, via integration of computational, cell-based and behavorial techniques.
Figure by Tamir Dingjan