The molecular basis of sex differentiation in mosquitoes

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Mosquitoes are vectors of some of our most deadly diseases. Broad-spectrum pesticides are routinely used to control mosquitoes, but with growing concerns about the impacts of these pesticides on our environment, we need to find new, species-specific methods of mosquito control. The long term goal of my research program is to develop new methods that prevent mosquitoes developing into disease-vectoring adults. As only female mosquitoes blood-feed and therefore transmit disease, we are particularly interested in disrupting female-specific developmental processes, with the goal of designing novel mosquito intervention strategies that have no adverse effects on non-target species. To find female-specific targets, we need to know considerably more about the sexual development of mosquitoes. Like many insects, a cascade of genes establishes the sex early in embryonic mosquito development. Sex differentiation then follows, ultimately producing females that can find hosts, blood-feed, and find ideal egg-laying sites. Males, in contrast, must find mates, feed only on nectar, and display complex courtship behaviours. The genes controlling the many sexually-dimorphic traits have not been well defined, with the exception of one master-switch gene, doublesex (dsx). In mosquitoes of the genus Aedes, which vector dengue and Zika viruses, DSX is thought to act as a transcription factor, regulating the expression of male or female genes, depending on whether the male (DSX-M) or the female (DSX-F) isoforms are present. Which genes are regulated by DSX is still largely unknown. Our short-term goals for this funding cycle are to 1) identify which genes are targeted by either DSX-M or DSX-F, 2) explore how the two isoforms perform different roles in each sex, and 3) examine how disrupting their functions affects sexual development. HQPs will be trained in a broad range of current molecular technologies, including transcriptomic techniques to identify DSX targets, gene-editing to examine how changes in DSX levels affect sexual development, and mass-spectrometry techniques to identify which proteins interact with each isoform of DSX, to uncover how sex-specific gene expression is regulated. Using the latest RNA sequencing technologies, they will examine when sex-specific RNA processing and gene expression occurs, to deduce when sexual differentiation begins in the mosquito's life. Finally, using RNA interference technologies, they will determine which genes can be targeted to prevent female larvae from developing into blood-feeding adults. Aedes aegypti is a disease vector of semitropical and tropical regions, while A. albopictus is an invasive species in North America that has reached Canada's borders. This proposed research will not only uncover aspects of the intriguing development of these mosquitoes, but will also provide a rich source of new molecular targets for the development of safer, more environmentally-friendly mosquito control technologies.