Novel high-throughput screens of Anopheles gambiae odorant receptors reveal candidate behaviour-modifying chemicals for mosquitoes

Authors

  • DAVID C. RINKER,

    1. Center for Human Genetics Research Training Program, Vanderbilt University Medical Centre, Nashville, Tennessee, U.S.A.
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    • These authors contributed equally to this study.

  • PATRICK L. JONES,

    1. Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, U.S.A.
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    • These authors contributed equally to this study.

  • R. JASON PITTS,

    1. Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, U.S.A.
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  • MICHAEL RUTZLER,

    1. Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, U.S.A.
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  • GRAY CAMP,

    1. Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, U.S.A.
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  • LUJUAN SUN,

    1. Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, U.S.A.
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  • PINGXI XU,

    1. Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, U.S.A.
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  • DANIEL C. DORSET,

    1. Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, U.S.A.
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  • DAVID WEAVER,

    1. Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, U.S.A.
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  • LAURENCE J. ZWIEBEL

    Corresponding author
    1. Center for Human Genetics Research Training Program, Vanderbilt University Medical Centre, Nashville, Tennessee, U.S.A.
    2. Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, U.S.A.
    3. Department of Pharmacology, Vanderbilt University Medical Centre, Nashville, Tennessee, U.S.A.
    4. Center for Molecular Neuroscience, Institute of Global Health and Program in Developmental Biology, Vanderbilt University Medical Centre, Nashville, Tennessee, U.S.A.
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Professor Laurence J. Zwiebel, Departments of Biological Sciences, and Pharmacology, Centres for Molecular Neuroscience, and Center for Human Genetics Research, Programs in Developmental Biology & Genetics, Institutes of Chemical Biology & Global Health, Vanderbilt University & Vanderbilt University Medical Centre, 6270 Medical Research Building III, 465 21st Avenue South, Nashville, Tennessee 37235, U.S.A. Tel.: +1 615 343 1894; e-mail: l.zwiebel@vanderbilt.edu

Abstract

Despite many decades of multilateral global efforts, a significant portion of the world population continues to be plagued with one or more mosquito-vectored diseases. These include malaria and filariasis, as well as numerous arboviral-associated illnesses, such as dengue and yellow fevers. The dynamics of disease transmission by mosquitoes is complex, and involves both vector competence and vectorial capacity. One area of intensive effort is the study of chemosensory-driven behaviours in the malaria vector mosquito Anopheles gambiae Giles, the modulation of which is likely to provide opportunities for disease reduction. In this context, recent studies characterize a large divergent family of An. gambiae odorant receptors (AgORs) that play critical roles in olfactory signal transduction. This work facilitates high-throughput, cell-based calcium mobilization screens of AgOR-expressing human embryonic kidney cells identifying a large number of conventional AgOR ligands, as well as the first nonconventional Orco (olfactory receptor co-receptor) family agonist. As such, ligand-mediated modulation serves as a proof-of-concept demonstration that AgORs represent viable targets for high-throughput screening and for the eventual development of behaviour-modifying olfactory compounds. Such attractants or repellents could foster malaria reduction programmes.

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