Severe malaria induces changes in circulating blood levels of the biogenic amines histamine and serotonin (5-hydroxytryptamine, 5-HT) and these changes are associated with human disease pathology. Histamine and 5-HT are also important neuromodulators in insects, including mosquitoes. Our 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 with our collaborators Dr. Michael Robert (Virginia Tech), who will provide modeling expertise, and Dr. Ed Lewis (University of Idaho), who will provide statistical expertise, we will establish 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.
One postdoctoral fellowship at the University of Idaho with Dr. Shirley Luckhart (annual salary $54,500 with full benefits and moving expenses)
In the Luckhart lab and with our collaborators, we will define 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. We will examine the effects of these treatments on the tendency to take a second bloodmeal, thermotolerance, fecundity, clutch size and lifespan. We will also identify the 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.
One postdoctoral fellowship at the University of Washington with Dr. Jeff Riffell (annual salary $57,100 with full benefits and moving expenses)
In the Riffell lab and with our collaborators, we will define how malaria-induced changes in biogenic amines impact the behavior and physiology of An. stephensi. Specifically, we will use innovative behavioral assays and neurophysiological methods to characterize how ingestion of histamine and 5-HT influences behavioral and neurophysiological responses to host cues. We will use a new real-time tracking system that allows quantification of behavior to host cues for mosquitoes under different pharmacological treatment conditions (agonist- or antagonist-fed blood meals, and infected or uninfected with P. yoelii). These studies will be combined with neurobiological experiments to determine whether (1) biogenic amines influence the sensitivity to host cues; and (2) whether using receptor antagonists for the biogenic amines can block enhanced sensitivity.
For these positions, please send your full CV, a cover letter describing your interest in the position and names/contact information for three professional references by email to the relevant PI (Dr. Luckhart sluckhart@uidaho.edu or Dr. Riffell jriffell@uw.edu). The positions are available immediately and open until filled.