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.