Food chemosensation: Characterization of novel bitter taste blockers and structure-function analysis

味觉是一种化学感觉系统，负责基本的食物评价，主要由细胞表面蛋白介导。人类能够识别几种基本的味道，包括甜、鲜、苦、酸、盐，可能还有脂肪。甜味、鲜味、苦味和脂肪的信号转导主要通过G蛋白偶联受体（gpcr）进行。在人类中，苦味感觉是由25个苦味受体（T2Rs）介导的，它们是GPCR家族中最大的亚群之一。然而，我们对它们的结构和功能知之甚少。到目前为止，大多数T2Rs的天然配体和阻滞剂（拮抗剂）的特性尚不清楚。

Taste is a chemosensory system responsible for basic food appraisal and is mediated mostly by cell surface proteins. Humans are capable of detecting a few basic tastes, which include sweet, umami, bitter, sour, salt, and possibly fat. The signal transduction for sweet, umami, bitter and fat tastes is predominantly through G protein-coupled receptors (GPCRs). In humans, bitter taste sensation is mediated by 25 bitter taste receptors (T2Rs), which form one of the largest sub-groups within the GPCR family. However, very little information on their structure-function is known. Thus far, the identities of natural ligands and blockers (antagonists) for majority of the T2Rs are unknown. OBJECTIVES The long-term objective of my NSERC program is to characterize the molecular basis of human bitter taste signal transduction. My approach will be to use a combination of molecular, cellular and biochemical techniques to discover novel T2R ligands and unravel their mechanisms of action. The short-term goals are: 1) Isolate and characterize novel ligands or bitter taste blockers isolated from food proteins. 2) Pursue structure-function studies on T2Rs. SIGNIFICANCE It is anticipated that the results from this research program would enable us to manipulate T2Rs so as to control the strength and duration of their signal. Knowledge about how T2Rs interact with their ligand will enable design of tastants that enhance food flavor. Bitter blockers can be used to suppress unpleasantness and thereby increase palatability of health-promoting bitter foods, such as fruit and vegetable extracts. The proposed research would train HQP, who will gain expertise in a broad range of modern biochemical and food chemosensory techniques.