The long-term goal of this project is to elucidate basic principles of chemosensory perception. It seeks to explain at the molecular and cellular level 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 and neurons, and of the functions that they perform. The project focuses on a family of 30 predicted chemosensory receptors, the IR20a clade, that are expressed in chemosensory neurons. The project considers a kind of chemical information that underlies one of the most ancient and fundamental of biological problems: how an animal recognizes a suitable mate of its own species. An understanding of the molecular and cellular basis of species recognition could lead to new means of controlling insects that transmit disease to humans.
The first aim examines two ionotropic receptors that are expressed in male neurons that are activated in a species-specific manner. The receptors in one species will be genetically replaced by their counterparts from another. The effects of this switch will be analyzed to test hypotheses about the molecular basis of species recognition.
The second aim considers another ionotropic receptor that may act in females as a detector of male cues. The role of this receptor and the neurons in which it is expressed will be analyzed in detail. The results may support a model in which these neurons act in a checkpoint: if they receive an appropriate cue, an acceptance signal is sent to the central nervous system.
The third aim capitalizes on an opportunity to analyze the role of a greatly understudied chemosensory organ, the wing. Different neurons on the wing are activated by different chemosensory cues, and an ionotropic receptor has been found to be expressed in a subset of these chemosensory neurons. The role of this receptor and the neurons in which it is expressed will be examined to determine if they are sensitive to species-specific cues. The results could provide a major advance in our understanding of a chemosensory organ whose function has remained speculative for 35 years.

Public Health Relevance

Insects transmit disease to hundreds of millions of people each year, and many of these insects rely on their chemosensory systems to identify their mates and their human hosts. This project is designed to reveal basic principles of insect chemoperception and to identify critical components of chemosensory systems. The results could be useful in developing new means of manipulating these systems and of thereby controlling insects that transmit disease to humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004729-18
Application #
9402076
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Sullivan, Susan L
Project Start
2001-01-01
Project End
2020-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
18
Fiscal Year
2018
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
Delventhal, R; Menuz, K; Joseph, R et al. (2017) The taste response to ammonia in Drosophila. Sci Rep 7:43754
He, Zhe; Carlson, John R (2017) Molecules That Can Rewire the Taste System. Biochemistry 56:6075-6076
Joseph, Ryan M; Sun, Jennifer S; Tam, Edric et al. (2017) A receptor and neuron that activate a circuit limiting sucrose consumption. Elife 6:
Delventhal, Rebecca; Carlson, John R (2016) Bitter taste receptors confer diverse functions to neurons. Elife 5:
Joseph, Ryan M; Carlson, John R (2015) Drosophila Chemoreceptors: A Molecular Interface Between the Chemical World and the Brain. Trends Genet 31:683-95
Stewart, Shannon; Koh, Tong-Wey; Ghosh, Arpan C et al. (2015) Candidate ionotropic taste receptors in the Drosophila larva. Proc Natl Acad Sci U S A 112:4195-201
Kwon, Jae Young; Dahanukar, Anupama; Weiss, Linnea A et al. (2014) A map of taste neuron projections in the Drosophila CNS. J Biosci 39:565-74
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
Delventhal, Rebecca; Kiely, Aidan; Carlson, John R (2014) Electrophysiological recording from Drosophila labellar taste sensilla. J Vis Exp :e51355
Ling, Frederick; Dahanukar, Anupama; Weiss, Linnea A et al. (2014) The molecular and cellular basis of taste coding in the legs of Drosophila. J Neurosci 34:7148-64

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