Lewis Hun Abstracts
Lewis Hun
Ph.D. Student
Entomology & Insect Science GIDP
American Society of Tropical and Hygiene (ASTMH)
Philadelphia, Pennsylvania
October 25-29, 2015
Professional Abstract
Lay Abstract
Malaria is one of the world’s most prevalent diseases. There are over 200 million annual clinical cases reported, and an estimated 660,000 deaths due to malaria each year. Of these fatalities, 77% are children under the age of five years. Despite current efforts to control malaria, the appearance of insecticide-resistant mosquitoes and drug-resistant parasite continues to accelerate the crisis of malaria transmission worldwide. Therefore, there is an urgent need for new innovative strategies to ease this burden. One strategy is to genetically engineer mosquitoes with better fitness and less parasites susceptible to replace the wild population. In mosquitoes, the insulin/insulin growth factor 1 signaling (IIS) cascade regulates lifespan, reproduction, and innate immunity. To better understand the impact of IIS in mosquitoes, we induced IIS in the fat body of transgenic A. stephensi mosquitoes by expressing an active form of A. stephensi Akt (AnsteAkt), a key component of the IIS cascade. The mosquito’s fat body is the main tissue responsible for antimicrobial production and has been shown to serve as “signaling center” for the IIS pathway. In early studies we found that Myr-AnsteAkt transcript and protein expression occurred in a fat body and blood meal specific manner, as expected for a transgene regulated by the vitellogenin promoter. Furthermore, we have been able to demonstrate increased activation of downstream IIS molecules indicating activation of the IIS cascade. We also observed changes in vitellogenin protein levels, but surprisingly did not observe any change in egg production. Most importantly, we observed a significant extension in the lifespan of the myr- AsteAkt transgenic A. stephensi. This increase in lifespan opens intriguing possibilities for manipulating the fitness of transgenic parasites resistant mosquitoes.
Mosquitoes are one of the world’s most severe public health concerns, killing nearly a million people annually. The impact of mosquito transmitted viruses such as malaria and dengue fever continues to increase as mosquitoes gain more resistance to the most promising insecticides. Thus, it is imperative to develop innovative mosquito control strategies to support more traditional control strategies as they become less effective. Traditional methods of mosquito control primarily rely on the use of insecticides designed to impact the immune, reproductive, or nervous system of insects. Unfortunately, many insecticides are associated with substantial risk to human health and the environment. The increased prevalence of malaria and dengue fever has led to the use of large quantities of insecticides to control the mosquito’s population. For example, DDT use to suppress the mosquito population in malaria endemic regions has resulted in increase insecticide in the environment.
In search of a novel strategy to reduce mosquito populations while curb the spread of malaria and use of insecticide, I am investigating how transgenic Anopheles stephensi mosquitoes are altered when insulin signaling is upregulated in the fat body during a bloodmeal. By manipulating the expression of key proteins in the IIS, we hope to impact the female’s lifespan and reproduction. Lifespan and reproduction are two key factors in determining the transmission efficiency of mosquito borne diseases. Finding a novel mechanism affecting these two physiological functions could be a valuable tool to control mosquito-borne disease transmission.