The long-term goal of this project is to elucidate basic principles of chemosensory perception. It seeks to explain at the molecular, cellular, and circuit levels how chemosensory information is encoded. The experimental plan takes advantage of the fruit fly Drosophila melanogaster as a model system, which allows incisive molecular genetic analysis of chemosensory receptors, neurons, and circuits, and of the functions they perform. The project considers a kind of chemical information that underlies one of the most ancient and fundamental of biological problems: how an animal detects a mate of its own species. A cluster of four ionotropic receptor genes, IR52a, IR52b, IR52c, and IR52d, the chemosensory neurons in which they are expressed, and the circuitry they activate will be analyzed to test hypotheses about their role in mate detection.
The first aim will provide a rigorous analysis of the expression and function of these genes in Drosophila melanogaster, as well as analyzing their counterparts from a related species. The experimental plan is designed to test hypotheses about the molecular logic of mate detection.
The second aim takes advantage of a recent advance in electrophysiology that allows new analysis of the cellular responses to pheromones. The proposed experiments are designed to provide pheromone-to-neuron and pheromone-to-receptor maps of a chemosensory organ.
The aim may also provide a new empty pheromone neuron system useful in analyzing pheromone receptors of a variety of species and in identifying compounds that activate or inhibit them.
The third aim exploits a new means of labeling neural circuits. It measures the responses of second-order neurons to pheromones. It also tests the hypothesis that pheromonal input from taste neurons is combined with olfactory input at an early stage of processing, before ultimately being translated into behavioral output. Diseases carried by insects afflict hundreds of millions of people each year. These insects detect their mates and their human hosts largely through their chemosensory systems. Advances in understanding these chemosensory systems may lead to new means of manipulating them and of thereby controlling these insect vectors of human disease.

Public Health Relevance

Insects transmit a wide variety of diseases to hundreds of millions of people each year, and the geographic ranges of some of these diseases have been increasing. Many of these insects rely on their chemosensory systems to identify their human hosts, their food, and their mates. This project is designed to elucidate how these systems operate and could lead to new means of manipulating them so as to control these insect vectors of disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC004729-21
Application #
10119529
Study Section
Chemosensory Systems Study Section (CSS)
Program Officer
Sullivan, Susan L
Project Start
2001-01-01
Project End
2025-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
21
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Koh, Tong-Wey; He, Zhe; Gorur-Shandilya, Srinivas et al. (2014) The Drosophila IR20a clade of ionotropic receptors are candidate taste and pheromone receptors. Neuron 83:850-65

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