The long-term goal of this project is to reveal the mechanisms by which odors are encoded, and to elucidate basic principles of the organization of the cells that encode them. The experimental plan takes advantage of the fruit fly Drosophila melanogaster as a model system, which allows powerful molecular genetic analysis of olfactory genes as well as physiological and behavioral analysis of olfactory function. The results may have major implications for the control of insects that transmit disease. The project focuses on a large family of Odorant binding proteins (Obps) that are remarkable in their number, diversity, and abundance. Despite their prominence, their role in the coding of odors is poorly understood.
The first aim i s to complete a map of the Drosophila antenna, in which all of the abundant Obps are mapped to the sensory hairs, or sensilla, in which odors are detected and encoded.
This aim i s designed to uncover organizational principles of a model olfactory organ and to lay a foundation for an incisive analysis of Obp function. The Obps will also be mapped to cell types with a view to testing specific hypotheses about the logic of their function.
The second aim proposes a strategic analysis of the role of an Obp in odor coding. The Obp-to-sensillum mapping has already identified a sensillum type that contains a single abundant Obp. The proposal capitalizes on this opportunity to examine the effects of depleting the sensillum of its sole abundant Obp. The analysis is designed to test hypotheses about the role of Obps in coding odor stimuli that vary in their temporal dynamics, identity and intensity. As a byproduct, the analysis should reveal new information about odor coding of stimuli that are common in nature but surprisingly understudied.
The aim could also lead to the establishment of a new "empty sensillum" system that would allow systematic analysis of Obps in a powerful way.
The third aim examines an unusual Obp with unique expression that is exceptionally well-conserved. Its localization suggests that it could act in the response to insect repellents such as DEET. The analysis is designed to characterize the expression of this Obp in detail and to test the hypothesis that its function is required for normal repulsion responses. A successful outcome could lead to new understanding of the mechanism of action of insect repellents and could suggest new means of insect control Diseases carried by insects afflict hundreds of millions of people each year, and these insects detect and locate their human hosts largely through olfaction. Advances in the understanding of olfaction may lead to new means of controlling these insect vectors of human disease. In particular, new insight into the molecular and cellular mechanisms by which insects respond to repellents may lead to the development of a new generation of insect repellents, with implications for the control of insect vectors and the diseases they transmit.

Public Health Relevance

Insects transmit a variety of devastating diseases, and many insect vectors of disease identify humans through their olfactory systems. This project is designed to reveal basic principles of insect olfaction and could be useful in developing new means of controlling insects that carry disease. The project may provide new insight into the molecular and cellular basis of olfactory response to the insect repellent DEET (N,N-Diethyl-meta-toluamide), and improved understanding of this response could lead to a new generation of insect repellents, with important implications for public health.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC002174-28
Application #
8759283
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Sullivan, Susan L
Project Start
1994-01-01
Project End
2019-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
28
Fiscal Year
2014
Total Cost
$352,729
Indirect Cost
$140,229
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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