A method for identifying sour-taste receptor ligands as well as compounds that modulate their activity

Unmet Need

The taste system is essential for feeding and survival as it helps humans evaluate the nutritional content in food. Every year, taste and smell dysfunctions affect more than 200,000 people, including those undergoing viral infections and chemotherapy. The resulting loss of appetite complicates the recovery and outcome of these patients. Researchers and clinicians wishing to manage taste dysfunction require extensive knowledge of taste receptors composition and research tools to study them, but they are often lacking. Sour taste receptors, for example, are critical for maintaining acid-base balance, yet their compositions and physiology were unknown. Additionally, sour taste is an attractive quality to modulate in food and pharmaceutical industries, whose global market is projected to reach over USD 16 billion in 2024. A high-throughput platform to study the mechanism of sour taste receptors and screen for compounds that can modulate their activity would be of considerable interest to both clinicians and industry researchers.

Technology

Duke inventors have reported a method for identifying sour-taste receptor ligands as well as compounds that modulate their activity. This valuable tool provides a platform for clinicians who study sour taste receptor physiology as well as food and pharmaceutical industries who wish to screen molecules that modulate sour taste sensation. Specifically, the inventors identified the heterologous PKD1L3 and PKD2L1 ion channels as sour taste receptors and created a fluorescence-based assay to monitor their activation in heterologous receptor-expressing cell lines. This technology has been used to successfully demonstrate sour taste receptor activity upon exposure to known acidic chemicals and validated with human and murine models.

Advantages

• First-in-class platform to study mechanism of sour taste in vitro and in vivo
• Easy, high-throughput method to screen for molecules that modulate sour taste receptor activity
• Complete technology comprising known biological targets, a heterologous cell line system, and a fluorescent-based assay