Novel strategies for killing mosquito disease vectors
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Aedes aegypti is the primary vector of dengue, Zika, chikungunya and yellow fever viruses. A native of sub-Saharan Africa, Ae. aegypti was imported to the Americas as part of the triangle trade between European powers, Africa (slaves), and the New World (plunder). Despite large-scale eradication campaigns mounted throughout the last century, Ae. aegypti maintains a wide distribution in the Americas. Mosquito-borne virus transmission results in substantial loss of quality of life as well as productivity (both through loss of workers through illness and increase medical costs). Control of Ae. aegypti relies on a combination of removing standing water, treating water with larvacides or predatory fish (when not possible to remove water), or treating with adulticides (fogs or residual sprays); these have so far been inadequate to control or prevent the transmission of important arboviruses. Additional control strategies based on the release of transgenic mosquitoes carrying a dominant lethal transgene (Oxitec), or sterilizing bacteria (Wolbachia) have recently been developed and are now being deployed in select locations. While effective at temporarily reducing mosquito populations, these new strategies rely on the continuous (perpetual) release of modified mosquitoes. Our overall objective is to continue the development of several new approaches to kill or otherwise control Ae. aegypti, taking advantage of recent gains in genomics and genome manipulation. Knowledge generated in our basic research program will be used to improve on existing sterile-insect approaches, build self-sustaining strategies, or develop entirely new modes of killing this mosquito to keep Ae. aegypti populations sufficiently low as to abrogate and prevent virus transmission. To accomplish this, we envision a limited number of conceptual approaches: sex manipulation (killing only females or converting females into males), developmental lethality (killing mosquitoes as embryos, larvae or pupae), or adult lethality (killing adults prior to, during or immediately after bloodfeeding). We will pursue all of these directions, and thus in the process seek to understand basic physiological processes in the mosquito vector such as bloodmeal digestion, iron detoxification, DNA repair, sex determination, salivary modulation of human immune responses, and the pupal-to-adult transition. Identifying and understanding the functional role of genes critical to each of these processes will feedback into attempts to construct genetics strains of Ae. aegypti that can be integrated into a mosquito control program.