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| |  Mosquitoes that spread malaria parasites use their sense of smell to find human hosts. Dr. Zwiebel is leading an international consortium of investigators that seeks to understand and ultimately interfere with the molecular basis of the insects' sense of smell. Their work seeks to develop safe, effective and low-cost products that would either repel mosquitoes or attract them to traps.
Focusing on the primary vector in Africa, Anopheles gambiae, investigators are using molecular technology to identify compounds that interfere with host-seeking and other behaviors that act by stimulating or blocking the responses of the mosquito’s odor receptors. Combining molecular, behavioral, and physiological approaches, the project team has made progress toward identifying novel chemicals that may act as mosquito repellants or attractants |
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| | | Identifying human odors and blends of odors that are essential for mosquito host recognition | | | | | Cloning and expressing genes that encode An. gambiae odor receptors in several heterologous and transgenic systems, and assessing the responses of these receptors to chemical stimuli associated with the insect’s behavior | | | | | Identifying novel compounds that activate or inhibit odor receptors in other systems | | | | | Assessing the ability of these compounds to affect mosquito behavior, both in the laboratory and in semi-field conditions | | |
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| | | Characterized a suite of human volatiles and odors that elicit strong olfactory responses in malaria vector mosquitoes. Using complex human odors from feet, hands, and skin, investigators have made progress toward establishing a working set of more than 90 odors that activate An. gambiae. They also have defined a preliminary "synthetic” human odor panel. | | | | | Made significant progress toward molecular cloning of genes for all An. gambiae odorant receptor proteins (AgORs), with 68 AgORs fully cloned into plasmid vectors. These efforts facilitate the rapid insertion and expression of AgORs in a triplicate array of laboratory platforms including Xenopus oocytes, Drosophila olfactory neurons, and mammalian HEK293 cells. | | | | | Advanced understanding of AgOR molecular biology and physiology within the An. gambiae olfactory apparatus with studies that have examined gender and tissue specific expression, molecular genetics, and odorant coding. | | | | | Worked toward pairing individual AgORs with human-derived and other odors that they specifically target, with one functional fly-based and 32 mosquito receptor screens completed and eight AgOR expressing cell lines established and validated. | | | | | Conducted chemical screens for novel compounds that over-stimulate, block, or otherwise interfere with AgOR activity to identify candidate behaviorally disruptive olfactory compounds (cBDOCs). | | | | | Used behavioral and physiological assays to monitor the effect of cBDOCs on mosquito behavior in both the laboratory and in semi-field systems in disease-endemic areas. | | |
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| | | Yale University, Connecticut, United States - US | | | | | Wageningen University, Netherlands - NL | | | | | Ifakara Health Research and Development Centre, Tanzania, United Republic of - TZ | | | | | Medical Research Laboratories, Gambia - GM | | |
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