Aedes aegypti mosquitoes transmit Dengue and Yellow Fever virus, and Culex quinquefasciatus mosquitoes transmit the West Nile virus and filarial parasite Wuchereria bancrofti to hundreds of millions of people. Methods for inhibiting vector- human contact, particularly in conjunction with other existing programs of vector control, may play a critical role in controlling the spread of these diseases. Female mosquitoes, like most other blood-feeding insects, identify their human hosts primarily using olfactory cues like carbon dioxide in exhaled breath, as well as other odors present in skin emanations. The goal of this research is to modify odor-guided host-seeking behavior of Aedes and Culex mosquitoes using cheap and environmentally safe odor molecules that can be used in very small quantities as effective trapping agents, masking agents and repellents. To achieve these goals we will focus on functional analyses of the CO2 sensing neuron. CO2 is detected in this neuron using a receptor comprising three members of the Gustatory receptor family that encode a highly conserved heteromeric CO2 receptor. We plan to use an integrated platform of neurophysiology, chemical- informatics, molecular, genetic and behavioral methods to;1) identify effective volatile agonists and antagonists for the CO2 receptors, 2) test the effects of these molecules on behavior of female Aedes and Culex mosquitoes, in particular, for the ability of antagonists in masking agents or repellents, and 3) agonists to improve trapping efficiency. In preliminary studies, we have identified a few volatile inhibitors and activators of the CO2 receptor in Aedes and Culex. We now propose to conduct further studies to identify more effective chemicals that inhibit or activate physiological and behavioral responses to CO2 in female mosquitoes. Successful completion of the proposed studies will lead to the development of a new generation of effective and safe insect repellents and lures that act by modifying CO2 receptor function.

Public Health Relevance

Aedes and Culex mosquitoes transmit several diseases including Dengue and lymphatic filariasis, and it is estimated that there are more than a hundred million people worldwide that are infected. Mosquitoes find their human hosts using the sense of smell. The goal of the proposed research is to modify odor-guided host-seeking behavior of Aedes and Culex mosquitoes using cheap and environmentally safe odor molecules that can be used in very small quantities as effective trapping agents, masking agents and repellents. Successful completion of the proposed studies will lead to the development of a new generation of effective and safe insect repellents and lures that act by modifying odor receptor function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI087785-05
Application #
8604359
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero, Adriana
Project Start
2010-02-01
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
5
Fiscal Year
2014
Total Cost
$376,200
Indirect Cost
$128,700
Name
University of California Riverside
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
MacWilliam, Dyan; Kowalewski, Joel; Kumar, Arun et al. (2018) Signaling Mode of the Broad-Spectrum Conserved CO2 Receptor Is One of the Important Determinants of Odor Valence in Drosophila. Neuron 97:1153-1167.e4
Clark, Jonathan T; Ray, Anandasankar (2016) Olfactory Mechanisms for Discovery of Odorants to Reduce Insect-Host Contact. J Chem Ecol 42:919-930
Ray, Anandasankar (2015) Reception of odors and repellents in mosquitoes. Curr Opin Neurobiol 34:158-64
Lacey, Emerson S; Ray, Anandasankar; Cardé, Ring T (2014) Close encounters: contributions of carbon dioxide and human skin odour to finding and landing on a host in Aedes aegypti. Physiol Entomol 39:60-68
Kain, Pinky; Boyle, Sean Michael; Tharadra, Sana Khalid et al. (2013) Odour receptors and neurons for DEET and new insect repellents. Nature 502:507-12
Tauxe, Genevieve M; MacWilliam, Dyan; Boyle, Sean Michael et al. (2013) Targeting a dual detector of skin and CO2 to modify mosquito host seeking. Cell 155:1365-79
Lacey, Emerson S; Cardé, Ring T (2012) Location of and landing on a source of human body odour by female Culex quinquefasciatus in still and moving air. Physiol Entomol 37:153-159
Turner, Stephanie Lynn; Li, Nan; Guda, Tom et al. (2011) Ultra-prolonged activation of CO2-sensing neurons disorients mosquitoes. Nature 474:87-91