DESCRIPTION (provided by applicant): Taste is the primary sensory system that determines whether a food or beverage will be ingested or rejected. Taste also influences the digestion and metabolism of food. Consequently, understanding the mechanisms underlying this sense is central to our ability to control intake of nutrients and modulate the excesses of consumption that contribute to diseases such as obesity, hypertension and the metabolic syndrome. These diseases pose serious problems for human health and have major negative economic impact worldwide, including in the United States and Russia. The long-term goal of the parent project is to positionally clone genes involved in taste and ingestive behavior. This involves developing genetically defined mouse models for genetic mapping and mechanistic studies. This FIRCA proposal will expand these studies to examine the role of sweet taste genes in postingestive endocrine responses to sweeteners. The proposed studies will aid in gene identification in mice, which will reveal the function of their human orthologs and their role in taste-related human behavior. This project will support collaboration between scientists at the Monell Center and the Pavlov Institute and will help to build research capabilities at the Pavlov Institute. The propose research will be done primarily in Russia at the Pavlov Institute of Physiology of the Russian Academy of Sciences in collaboration with Dr. Zolotarev as an extension of NIH grant R01DC000882 (09/19/2008 - 08/31/2013). PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page

Taste often determines whether a food or beverage will be ingested; thus, understanding this sense is central to modulating the excess consumption that can underlie such serious worldwide diseases as obesity, hypertension and the metabolic syndrome. The goal of the parent project and this FIRCA proposal is to identify taste-related genes in mice, which will suggest the function of their human orthologs and their role in taste-related human behavior. These studies, when completed, may provide important new avenues for interventions designed to modify excess food consumption. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page