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.
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.
| 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 |
