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

味觉是一种化学感受系统，主要由细胞表面蛋白介导，负责基本的食物评价。人类能够检测一些基本的味道，包括甜，鲜味，苦，酸，盐，可能还有脂肪。甜味、鲜味、苦味和脂肪味的信号转导主要通过G蛋白偶联受体（GPCR）进行。在人类中，苦味感觉由25种苦味受体（T2 R）介导，其形成GPCR家族中最大的亚组之一。然而，关于其结构-功能的信息很少。到目前为止，大多数T2 R的天然配体和阻断剂（拮抗剂）的身份是未知的。 目标 我的NSERC计划的长期目标是表征人类苦味信号转导的分子基础。我的方法将是使用分子，细胞和生物化学技术的组合来发现新的T2 R配体，并解开其作用机制。短期目标是：1）分离和表征从食物蛋白质中分离的新型配体或苦味阻断剂。2)对T2 R进行结构-功能研究。 意义 预计这项研究计划的结果将使我们能够操纵T2 R，以控制其信号的强度和持续时间。关于T2 R如何与它们的配体相互作用的知识将使得能够设计增强食品风味的促味剂。苦味阻断剂可用于抑制不愉快，从而增加促进健康的苦味食物（如水果和蔬菜提取物）的适口性。拟议的研究将培训HQP，他们将获得广泛的现代生物化学和食品化学传感技术的专业知识。

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.