Chemosensory responses are critical components that direct 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 selection behavior 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 Nile virus encephalitis. Within this context, I have undertaken a molecular examination of several elements of the olfactory signal transduction cascade in the principal African malaria vector mosquito Anopheles gambiae sensu stricto, where a significant preference for human hosts (anthropophily) underlies its inherent ability to transmit human malaria. An increased understanding of olfactory mechanisms and their underlying chemical cues in this system may provide insight in the processes of insect behavioral responses in general and vector disease transmission in particular. Moreover, this study would likely be instrumental in the development of novel mosquito control strategies targeted against this broad family of disease vectors, as well as other insects that pose considerable medical and economic threats through their ability to transmit disease and to act as agricultural pests. The objectives of this proposal complements ongoing studies in the laboratory of olfactory arrestins in A.gambiae and focus on an examination of a family of candidate odorant receptor proteins in A. gambiae (AgORs) that has recently been identified by this laboratory. Thus far, we have identified 44 candidate AgORs and have performed an initial characterization of a small subset of this gene family. While the exact number of potential AgORs remain to be established in A. gambiae, we proposed to begin a systematic analysis of this gene family by completing several studies focusing on their expression in the mosquito. Initially, in order to establish a strategic plan for future studies, we will employ a variety of molecular approaches to identify AgOR family members that exhibt sex-specific expression patterns. These AgORs will form our primary focus group for subsequent characterization of the developmental, spatial and temporal expression pattems of AgORs. In addition, in an extension of initial studies that specifically targets AgOR's role in the olfactory processes that underlie disease transmission, will we propose to conduct a series of detailed experiments to examine the temporal kinetics of AgOR expression in response to blood feeding.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Special Emphasis Panel (ZRG1-TMP (99))
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Costero, Adriana
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Vanderbilt University Medical Center
Schools of Arts and Sciences
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Pitts, R Jason; Derryberry, Stephen L; Zhang, Zhiwei et al. (2017) Variant Ionotropic Receptors in the Malaria Vector Mosquito Anopheles gambiae Tuned to Amines and Carboxylic Acids. Sci Rep 7:40297
Rinker, David C; Pitts, R Jason; Zwiebel, Laurence J (2016) Disease vectors in the era of next generation sequencing. Genome Biol 17:95
Suh, Eunho; Choe, Dong-Hwan; Saveer, Ahmed M et al. (2016) Suboptimal Larval Habitats Modulate Oviposition of the Malaria Vector Mosquito Anopheles coluzzii. PLoS One 11:e0149800
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
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
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
Suh, Eunho; Bohbot, Jonathan; Zwiebel, Laurence J (2014) Peripheral olfactory signaling in insects. Curr Opin Insect Sci 6:86-92
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
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
Rinker, David C; Zhou, Xiaofan; Pitts, Ronald Jason et al. (2013) Antennal transcriptome profiles of anopheline mosquitoes reveal human host olfactory specialization in Anopheles gambiae. BMC Genomics 14:749

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