Mosquitoes are vectors of pathogens and arboviruses, including malaria, dengue, chikungunya, West Nile virus, and the Zika virus. With the growing concerns regarding insecticide spraying into the environment and given the increasing cases of mosquitoes? resistance to pesticides, environmentally friendly strategies for monitoring, surveillance, and controlling populations of mosquitoes are sorely needed. One such strategy is the use of oviposition attractants as lures for surveillance, monitoring, and potentially controlling mosquito populations when combined with a toxic agent. This project is aimed at advancing our understanding of the molecular basis of mosquito olfaction, specifically, how inhibitory compounds may interfere with the reception of oviposition attractants and other odorants, and at using odorant receptors to guide isolation and identification of oviposition attractants from natural sources. The proposed research will strengthen existing collaboration among vector biologists addressing fundamental questions in olfaction and those with hands-on experience, including colleagues involved in controlling populations of the southern house mosquito and the invasive yellow fever mosquito in areas where the Zika virus is currently causing or threatens to cause an infectious epidemic.
In Aim #1, we will investigate both whether agonists and inhibitory compounds act on different binding sites of ?inhibitory? odorant receptors (ORs) and the mechanism(s) of receptor inhibition.
Aim #2 will address whether ORs, including ?inhibitory? ORs, are co-expressed in antennal neurons, and whether these ?inhibitory? receptors affect the behavior of neurons, particularly those responding to oviposition attractants.
In Aim #3, we will search the genomes of the yellow fever mosquito and the southern house mosquito for orthologs and other ?inhibitory? receptors.
In Aim #4, we will use odorant receptors, particularly those sensitive to oviposition attractants, to prospect for novel attracts from natural sources, including essential oils and extracts from conspecific larvae. OR-guided isolation of active ingredients will be followed by chemical characterization and synthesis. The new lures will be tested first in indoor behavioral assays and subsequently in the fields in Clovis, California and in Recife, Brazil, the epicenter of the Zika epidemic.

Public Health Relevance

Environmentally friendly strategies for monitoring, surveillance, and controlling populations of mosquitoes are sorely needed, particularly now that the Zika virus is spreading so rapidly in South and Central America and threatens to cause an epidemic in the United States. This project is aimed at advancing our understanding of the molecular basis of mosquito olfaction, specifically, how inhibitory compounds may interfere with the reception of oviposition attractants and other odorants, and at using an odorant receptor-guided strategy for the isolation and identification of oviposition attractants from natural sources to develop new lures for trapping gravid female mosquitoes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI095514-06A1
Application #
9441635
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2011-12-01
Project End
2022-05-31
Budget Start
2018-06-06
Budget End
2019-05-31
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Davis
Department
Zoology
Type
Earth Sciences/Resources
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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Hughes, David T; Pelletier, Julien; Rahman, Suhaila et al. (2017) Functional and Nonfunctional Forms of CquiOR91, an Odorant Selectivity Subunit of Culex quinquefasciatus. Chem Senses 42:333-341
Pelletier, Julien; Xu, Pingxi; Yoon, Kyong S et al. (2015) Odorant receptor-based discovery of natural repellents of human lice. Insect Biochem Mol Biol 66:103-9
Yin, Jiao; Choo, Young-Moo; Duan, Hongxia et al. (2015) Selectivity of odorant-binding proteins from the southern house mosquito tested against physiologically relevant ligands. Front Physiol 6:56

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