Aedes aegypti is the main vector of dengue, yellow fever and chikungunya viruses, and is a model system for studies of other mosquitoes that vector arboviruses. The acquisition of a bloodmeal is by nature a high-risk, high reward activity for the mosquito- virtually unlimited resources to fuel egg production, combined with extraordinarily high levels of iron which must be detoxified to prevent free-radical production andoxidative damage. In contrast, blood-derived iron is both an essential micronutrient for egg production and development as well as a critical signaling molecule to initiate the vitellogenic process. Thus, a fine balance exists between iron overload and iron deficiency, achieved through a highly structured system of iron import, export and storage. In this proposal, we aim to identify and disrupt mosquito transport proteins involved in the cellular uptake of both molecular iron and heme using a combination of high-throughput sequencing (aim 1) and targeted gene editing (aim 2) technologies. The identification of mosquito iron import proteins would provide unique targets for vaccine, drug, or transgenic strategies aimed at disrupting mosquito vectorial capacity, as critical importers/exporters present on the lumenal surface of the digestive tract would be exposed to potential chemical inhibitors or neutralizing antibodies if present in the bloodmeal.

Public Health Relevance

Aedes aegypti is the main vector of dengue; yellow fever and chikungunya viruses; and is a model system for studies of other mosquitoes that vector arboviruses. The molecular mechanisms for heme import in insects; including bloodfeeding mosquitoes such as Ae. aegypti; remain completely unknown. The identification of mosquito heme importer proteins would provide unique targets for vaccine; drug; or transgenic strategies aimed at disrupting mosquito vectorial capacity and hence interrupting disease transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21AI115138-03
Application #
9385853
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2016-11-01
Project End
2018-03-31
Budget Start
2016-11-01
Budget End
2018-03-31
Support Year
3
Fiscal Year
2016
Total Cost
$182,645
Indirect Cost
$57,645
Name
Texas A&M Agrilife Research
Department
Type
Domestic Higher Education
DUNS #
847205713
City
College Station
State
TX
Country
United States
Zip Code
77843
Whiten, Shavonn R; Ray, W Keith; Helm, Richard F et al. (2018) Characterization of the adult Aedes aegypti early midgut peritrophic matrix proteome using LC-MS. PLoS One 13:e0194734
Tsujimoto, Hitoshi; Anderson, Michelle A E; Myles, Kevin M et al. (2018) Identification of Candidate Iron Transporters From the ZIP/ZnT Gene Families in the Mosquito Aedes aegypti. Front Physiol 9:380
Whiten, Shavonn R; Eggleston, Heather; Adelman, Zach N (2017) Ironing out the Details: Exploring the Role of Iron and Heme in Blood-Sucking Arthropods. Front Physiol 8:1134