Defining the antiviral impacts of Wolbachia in Aedes aegypti mosquitoes

The World Mosquito Program (WMP; based at Monash University) has pioneered a novel biocontrol tool, Wolbachia, that controls the transmission of mosquito borne viruses such as dengue and Zika. A recent randomised controlled trial in Indonesia demonstrated the efficacy of this method, with Wolbachia-treated regions measuring a 77% reduction in dengue incidence compared to untreated regions (Utarini et al., NEJM 2021). WMP has projects operating in 12 countries around the world, including in the Pacific, South East Asia and South America and aims to rapidly scale to protect people living at risk of these diseases. The intervention is centred around the endosymbiotic bacterium Wolbachia which is found in up to 60% of insect species. Wolbachia is effectively maintained in insect populations as it is maternally inherited and can provide a reproductive advantage to insects that are infected. It's not naturally found in Ae. aegypti, the major vector for dengue and Zika, but can be artificially introduced. Importantly, Wolbachia's reproductive impacts allow it to be stably maintained in wild mosquito populations following an initial release period of Wolbachia-Ae. aegypti. Despite the immense success of Wolbachia as a biocontol tool, it is still not clear how Wolbachia interferes with viruses like dengue and Zika. Three main hypotheses include- 1) Wolbachia competes with viruses for space in mosquito cells 2) Wolbachia modifies host gene expression to create a state incompatible with virus replication 3) Wolbachia is a nutritional parasite that reduces the availability of host resources also required by viruses This project will use a range of molecular techniques, including RNAseq and lipidomics, and a novel set of Wolbachia-infected mosquitoes and mosquito-derived cell lines, to define the cellular changes induced by Wolbachia. Students will gain experience in a range of cell culture, virology and entomology techniques and have the opportunity to work alongside experts from the World Mosquito Program. Outcomes of this study will be published in high impact journals and will provide an important contribution to the evidence base and longevity of this significant health intervention.