| Summary: | Aedes aegypti and Aedes albopictus are the primary vectors of dengue (DENV) and chikungunya (CHIKV) viruses, causing millions of infections annually. Novel genetic mosquito control methods are being trialled, including population replacement using disease refractory mosquitoes transinfected with the intracellular bacterial endosymbiont Wolbachia, and population suppression by release of male mosquitoes carrying self-limiting genes. The underlying cause of Wolbachia-induced DENV refractoriness is unconfirmed. In Chapter 2, I examine in Ae. albopictus the hypothesis that reactive oxygen species (ROS) induced immune activation plays a role, but neither ROS nor innate immune pathways were upregulated. In Chapter 3, an untargeted analysis of the Ae. albopictus lipidome showed it is significantly altered by Wolbachia infection, highlighting sphingolipids as candidates for future investigations into DENV-refractoriness. Genetic constructs for population suppression are better characterised than Wolbachia-host interactions but incompletely described modes of action and reliance on random genome integration to control expression fails to take full advantage of engineering approaches to design optimal genetic control phenotypes. In Chapter 4, I engineer female-specific, late-acting lethality in Ae. aegypti using specific effectors crossed with candidate pupal-stage promoters and a doublesex cassette causing sexspecific splicing. In Chapter 5, I transform and characterise Ae. aegypti lines producing sex-specific Drosophila melanogaster alcohol dehydrogenase (Adh) to evaluate potential for early-stage inducible genetic sexing. No effective lines were produced but I suggest future design alterations. Overall, this thesis contributes to understanding the molecular mechanisms underlying two distinct genetic control strategies in Aedes mosquitoes. It promotes the use of that mechanistic knowledge to engineer optimal traits for control and for improving mass-rearing methods to meet the clear need for effective and economical area-wide control of arbovirus vectors.
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