Analysis of a Large Family of Candidate Taste Receptors

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DESCRIPTION (provided by applicant): The long-term goal of this project is to reveal the logic by which tastants are encoded, and to elucidate basic principles of the organization and development of the neurons that encode them. The experimental plan takes advantage of the fruit fly Drosophila melanogaster as a model system, which allows incisive molecular genetic analysis of taste genes as well as physiological analysis of taste function. The first aim is to complete a functional analysis of a numerically simple model taste organ, the foreleg. The taste neurons of this organ have been defined and all members of the Gr family of taste receptors have been mapped to them. Physiological responses of this organ to sugars, bitter compounds and amino acids will be analyzed with a view to understanding the role of this organ in the evaluation of taste. The analysis is designed to address the problem of how a sensory system integrates the multiple inputs that are ultimately translated into a behavioral response. The results may support a model explaining how the animal makes a decision critical to all animals: whether to accept or reject a potential food source. The underlying basis of feeding regulation has major implications for public health. The second aim addresses the role of G proteins in taste neuron signaling and development. The role of these proteins in chemosensory signaling is a central question in the field. The analysis will test the hypothesis that complete removal of certain G proteins leads to a complete loss of physiological response to either sugars or bitter compounds. The hypothesis that these proteins act in the development of taste neurons will also be tested. The third aim is to examine the function of a bitter receptor by expressing it in cells that have no bitter response. The analysis is designed to test the hypothesis the certain members of the Gr family act as co-receptors for other members. It is also designed to determine whether an efficient system can be constructed for the study of bitter receptors and for the identification of tastants that activate or inhibit them. The results could yield a wealth of new opportunities to study the function of bitter receptors and their role in the perception of bitter taste. Diseases carried by insects afflict hundreds of millions of people each year, and these insects receive taste cues from their human hosts. Advances in the understanding of taste may lead to new means of controlling these insect vectors of human disease. In particular, the identification of compounds that activate or inhibit bitter taste receptors could provide new agents for the control of insect vectors and the diseases they transmit. PUBLIC HEALTH RELEVANCE: Insects transmit disease to hundreds of millions of people each year, and many insect vectors of disease identify humans through their chemosensory systems. This project is designed to reveal basic principles of insect chemosensation and could be useful in developing new means of controlling insects that carry disease. The project also concerns the molecular and cellular basis of a decision, whether to accept or reject a potential food source, which is made by all animals and which has important implications for public health.