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Last Updated: 13/01/2023
Biogenic amines, malaria and manipulation of mosquito physiology and behavior
Objectives
- To define and model the scope of effects of ingested histamine and 5-HT, alone and in combination at concentrations that reflect malaria-associated and healthy blood levels, on Anopheles stephensi infection success with Plasmodium falciparum and with the mouse parasite Plasmodium yoelii yoelii 17XNL.
- To define the effects of ingested histamine and 5-HT, alone and in combination, on visual and olfactory physiology in An. stephensi by using antennal and retinal recordings and behavioral bioassays.
- To quantify endogenous histamine and 5-HT in An. stephensi and map associated histaminergic and serotonergic gut-to-brain signaling networks. Also, identify and model effects of ingested biogenic amines on levels of endogenous biogenic amines and use histamine and 5-HT receptor antagonists to interrupt signaling control of malaria parasite infection, tendency to take a second bloodmeal and reproduction in An. stephensi.
Histamine and 5-HT are also important neuromodulators in insects, including mosquitoes. The overarching hypothesis is that histamine and 5-HT, ingested in blood by feeding mosquitoes, signal through anopheline biogenic amine receptors and alter endogenous biogenic amine levels, life history traits, behavior and mosquito infection success to amplify malaria parasite transmission. These studies are innovative in that they connect novel mosquito biology to clinical observations in malaria, they focus on mosquito ingestion of biogenic amines at physiological levels detected in blood and they will define previously unexplored anopheline gut-brain axes for histaminergic and serotonergic signaling.
With completion of these studies, It will be established that biogenic amine concentrations associated with severe malaria and ingested by feeding mosquitoes can alter mosquito physiology and biology in patterns that would be predicted to favor parasite transmission. Such knowledge can be used in the future to connect transmission control to clinical interventions (e.g., to reduce elevated histamine and reverse declines in 5-HT to mitigate human malarial disease) and for future development of novel lures to manipulate biogenic amine signaling in vector mosquitoes.
Aug 2022 — Jul 2026
$556,756
