Biogenic amines, malaria and manipulation of mosquito physiology and behavior

Active Project Grant Awarded Last action

Award ID
R01AI165481
Recipient
Awarding agency
Obligated
$3,286,123

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 85% complete
Originally
Place of performance
Moscow, ID 83844, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
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. We will address our overarching hypothesis with three specific aims. In aim 1, we will 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 an. Stephensi infection success with plasmodium falciparum and with the mouse parasite plasmodium yoelii yoelii 17XNL. We will also examine the effects of these treatments on the tendency to take a second bloodmeal, thermotolerance, fecundity, clutch size and lifespan. In aim 2, we will use antennal and retinal recordings and behavioral bioassays to define the effects of ingested histamine and 5-HT, alone and in combination, on visual and olfactory physiology in an. Stephensi. In aim 3, we will quantify endogenous histamine and 5-HT in an. Stephensi and map associated histaminergic and serotonergic GUT-to-brain signaling networks. We will 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. With completion of these studies, 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.

Transactions

Action Obligated Date
Amendment $0
Amendment $542,303
Amendment $541,212
Amendment $544,548
Amendment $544,548
Amendment $556,756
Original award $556,756

Subawards

Subrecipient Amount Awarded
University Of Washington Statement of Work Our goal is to understand how malaria-induced changes in biogenic amines impacts the behavior and physiology of the Anopheles stephensi… $820,916

Quick answers

Who received award R01AI165481?

R01AI165481 was awarded to Regents Of The University Of Idaho by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 8, 2022.

How much is award R01AI165481 worth?

$3,286,123 has been obligated on R01AI165481.

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