Analysis of Chemosensory Receptor Genes

PROJECT SUMMARY
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.

Grant Number: 5R01DC004729-25
NIH Institute/Center: NIH
Principal Investigator: John Carlson