Our projects
Mechano-Wolbachia: Uncovering mechanisms of action of antiviral bacterium
Funding: ERC Starting Grant 2021


Animals and microbes interact in intricate ways. Wolbachia, a common intracellular insect symbiont, can manipulate reproduction and protect hosts from viruses. Thus, Wolbachia is an asset in the control of insectborne diseases. However, as Wolbachia cannot be cultured outside of host cells or genetically manipulated, the mechanisms of its antiviral phenotype remain poorly understood, and this inhibits wider exploitation. I have been working to remedy these deficiencies, and now stand poised to discover the mechanisms of
Wolbachia-conferred antiviral protection by answering the following questions:
1) Where does the protection originate? Up to now, mechanisms of protection have been studied in whole organisms, often lacking resolution, or in cultured cells, which lack emergent properties. I will identify tissues and cell types of the host where protection starts. To do this, I will: a) quantify titers of Wolbachia and virus at early time points post-viral infection in insect tissues, b) measure gene expression of host and microbes to identify candidates for further molecular characterisation, and c) test the extent of the utility of widely adopted, yet unvalidated, cell-culture models of antiviral protection.
2) Which Wolbachia genes effect protection? Wolbachia research has historically been impeded by a lack of tools to study gene function. Here, I will deploy antisense technology, which I have recently developed, to interrogate function of candidate Wolbachia genes in the native system. I will also engineer new methods to target Wolbachia genes and proteins, based on my data on cell-penetrating peptide-mediated delivery of bioactive cargo to Wolbachia.
This project has two major outcomes: it will uncover Wolbachia factors responsible for Wolbachia-conferred antiviral protection, and it will transform Wolbachia and symbiosis research by creating tools to study symbiont gene function.
Image-Wolbachia: Understanding Wolbachia and Wolbachia-conferred antiviral protection in dengue virus vector
Funding: ISIDORe/InfraVec2



Wolbachia is an insect-associated maternally transmitted antiviral bacterium. It has been artificially transferred – transinfected - from Drosophila to dengue vector Aedes aegypti. These mosquitoes are currently being deployed in successful programmes aiming at limiting dengue burden in humans. Although Wolbachia can be transferred between non-crossing species and blocks human-pathogenic virus replication, the mechanisms and structures enabling these phenotypes remain unknown.
In this project, we will ask which tissues are crucial for Wolbachia-conferred antiviral protection in Ae. aegypti mosquito. Next, we will test a specific hypothesis regarding molecular structures necessary for Wolbachia transinfection and horizontal transmission in the wild.