To understand the role of IIS on lifespan and immunity we have genetically engineered key components of the IIS cascade into mosquitoes in a tissue specific manner. Specifically, we have overexpressed the IIS activator Akt and the IIS inhibitor PTEN into the mosquitoes midgut and fat body. We then test these transgenic mosquitoes against non-transgenic control mosquitoes to determine if increased or decreased IIS in a given tissue impacts lifespan or alters the mosquito’s ability to transmit the human malaria parasite Plasmodium falciparum. This work is a collaborative project with researchers at the University of California - Davis and the University of Georgia and is funded by a grant from the National Institutes of Health.
Disrupting the IIS cascade to enhance reproduction:
The IIS cascade is also a key regulator of reproduction. It controls steroidogenesis in the ovaries and vitellogenesis in the fat body. Using RNA interference we knocked down expression of the IIS inhibitor PTEN in the fat body and ovaries, thereby increasing insulin signaling. We observed up to a 63% increase in egg production in mosquitoes with increased IIS. We are in the process of generating transgenic mosquitoes with increased and decreased insulin signaling in either the fat body or the ovary to determine which tissue is more important to the regulation of reproduction by insulin signaling. By understanding how insulin signaling regulates reproduction we may be able to control mosquito population. Alternatively, increased reproduction may be a viable mechanism for replacing wild mosquito populations with ones incapable of transmitting disease. This work is being funded by the Bill and Melinda Gates Foundation.
Determining the age structure of Aedes aegypti populations in the Southwestern US:
The yellow fever mosquito Aedes aegypti is an important vector of dengue and dengue hemorrhagic fever, a virus that infects and sometimes kills thousands annually. Although this mosquito is found in the Southwestern US, including Southern Arizona, the disease is not currently found in the US. One possibility for this is that Aedes aegypti mosquitoes at the edge of their ecological range do not survive long enough to transmit the dengue virus. To examine this we are attempting to identify genes in the mosquito that can be used as markers of chronological and physiological aging. We have currently identified one such gene and verified its ability to accurately age mosquitoes under laboratory and semi-field conditions. In addition, we have verified the accuracy of this gene on field collected mosquitoes by comparing the predicted mosquito age with the reproductive status of the mosquito. Young mosquitoes that have not yet taken a blood meal and produced a clutch of eggs have tightly coiled trachea on their ovaries that unfurl as the ovaries increase in size during egg production. Mosquitoes with tightly coiled trachea were consistently aged less than six days old with our aging gene marker compared with an average of 15 days old. This pilot project is a collaborative effort with other researchers at UA and is supported by the Center for Insect Science.