Chemosensory responses are critical components in the control of several essential behaviors of insects that are vectors for pathogens responsible for many important human diseases. In particular, olfaction plays a major role in host seeking and oviposition selection behaviors of blood-feeding female mosquitoes and, as such, constitutes a critical component of the mosquito's ability to transmit diseases such as malaria, dengue, yellow fever and West Nile virus encephalitis. Within this context, and together with our colleagues, we have undertaken a molecular and cellular examination of several elements of the olfactory signal transduction cascade in the principal African malaria vector mosquito Anopheles gambiae sensu stricto and the arbovirus vector Aedes aegypti. An increased understanding of olfactory mechanisms and their underlying chemical cues in these systems may provide insight into the processes of insect behavioral responses in general and disease transmission by vectors in particular and would likely be instrumental in the development of novel mosquito control strategies. We have made significant progress in the characterization of several aspects of olfactory process in both mosquito systems leading to, among other things, the identification and initial characterizations of a family of odorant receptor proteins in An. gambiae (AgORs) and Ae. aegypti (AaORs) that lie at the heart of the olfactory signaling pathway. Building on those advances, this proposal for competitive renewal focuses on extending several elements of our ongoing program including characterization of: (1) structure/function relationships between AgORs and AaORs, (2) the role of AgORs and cognate odorant binding proteins (AgOBPs) in the context of larval olfaction and odor coding in vivo and (3) the molecular events underlying oviposition site selection by gravid adult females.

Public Health Relevance

We have undertaken a molecular and cellular examination of elements of the sense of smell (olfaction) that largely drive several important behaviors in malaria and arbovirus vector mosquitoes. An increased understanding of olfactory mechanisms and their underlying chemical cues in these systems may provide insight into the processes of mosquito behavioral responses and disease transmission by vectors. This information would likely be instrumental in the development of novel mosquito control strategies. Thus far, we have made significant progress and now propose to extend, our characterization of several aspects of olfactory process in both mosquito systems that focus on the role and interactions of a large family of odorant receptor proteins in An. gambiae (AgORs) and Ae. aegypti (AaORs) that lie at the heart of the olfactory signaling pathway.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI056402-08
Application #
8305055
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero, Adriana
Project Start
2003-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
8
Fiscal Year
2012
Total Cost
$493,213
Indirect Cost
$177,051
Name
Vanderbilt University Medical Center
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Pitts, R Jason; Derryberry Jr, Stephen L; Pulous, Fadi E et al. (2014) Antennal-expressed ammonium transporters in the malaria vector mosquito Anopheles gambiae. PLoS One 9:e111858
Zhou, Xiaofan; Rinker, David C; Pitts, Ronald Jason et al. (2014) Divergent and conserved elements comprise the chemoreceptive repertoire of the nonblood-feeding mosquito Toxorhynchites amboinensis. Genome Biol Evol 6:2883-96
Pitts, R Jason; Liu, Chao; Zhou, Xiaofan et al. (2014) Odorant receptor-mediated sperm activation in disease vector mosquitoes. Proc Natl Acad Sci U S A 111:2566-71
Romaine, Ian M; Taylor, Robert W; Saidu, Samsudeen P et al. (2014) Narrow SAR in odorant sensing Orco receptor agonists. Bioorg Med Chem Lett 24:2613-6
Hughes, David T; Wang, Guirong; Zwiebel, Laurence J et al. (2014) A determinant of odorant specificity is located at the extracellular loop 2-transmembrane domain 4 interface of an Anopheles gambiae odorant receptor subunit. Chem Senses 39:761-9
Kumar, Brijesh N; Taylor, Robert W; Pask, Gregory M et al. (2013) A conserved aspartic acid is important for agonist (VUAA1) and odorant/tuning receptor-dependent activation of the insect odorant co-receptor (Orco). PLoS One 8:e70218
Liu, Chao; Zwiebel, Laurence J (2013) Molecular characterization of larval peripheral thermosensory responses of the malaria vector mosquito Anopheles gambiae. PLoS One 8:e72595
Pask, Gregory M; Bobkov, Yuriy V; Corey, Elizabeth A et al. (2013) Blockade of insect odorant receptor currents by amiloride derivatives. Chem Senses 38:221-9
Rinker, David C; Pitts, R Jason; Zhou, Xiaofan et al. (2013) Blood meal-induced changes to antennal transcriptome profiles reveal shifts in odor sensitivities in Anopheles gambiae. Proc Natl Acad Sci U S A 110:8260-5
Pask, Gregory M; Romaine, Ian M; Zwiebel, Laurence J (2013) The molecular receptive range of a lactone receptor in Anopheles gambiae. Chem Senses 38:19-25

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