Our group studies the molecular mechanisms that shape the transmission, emergence and pathogenesis of flaviviruses.
The Flavivirus family of viruses includes some of the most significant mosquito-borne viruses affecting humans, including dengue virus, yellow fever virus and Zika virus. Dengue virus can cause a life-threatening haemorrhagic disease and is the most prevalent human arthropod-borne virus, with the number of cases doubling every decade since 1990 and half the world’s population now living in at-risk areas. Zika virus can cause severe developmental disorders and emerged in the Americas in 2015, causing a global public health emergency. There are no antiviral therapies to treat any flaviviral diseases, and even though vaccines exist for dengue virus and yellow fever virus, both viruses continue to cause severe disease outbreaks.
The major vector for these flaviviruses is the tropical mosquito Aedes aegypti, which thrives in urbanised environments and has a strong preference for feeding on humans. If we could develop new methods for making Aedes aegypti less able to transmit viruses, we would be able to broadly protect humans from the wide range of viruses transmitted by this mosquito, including viruses that may emerge in the future. However, to achieve this goal, we need a better fundamental understanding of how flaviviruses interact with Aedes aegypti at the molecular level.
Our overarching goal is to expand the repertoire of research tools available to study Aedes aegypti, and to use these tools to define in detail the molecular interactions between flaviviruses and their mosquito vector. We focus primarily on fundamental questions about mosquito biology in laboratory and field settings. The information we gain could eventually be used to develop new ways of modifying mosquito vectors to prevent disease transmission.
There are three major ongoing research topics in our group.
- How are flaviviruses detected by the mosquito immune system?
The mosquito immune system is a strong barrier to disease transmission because it can reduce the ability of a virus to replicate in its vector. We are working towards identifying which specific molecules associated with flavivirus infection can be detected by the mosquito immune system. We are also characterising what mosquito factors and pathways are involved in the detection of these viral molecules.
- How do flaviviruses interfere with the mosquito immune system to enhance viral replication and transmission?
To cause disease, or be transmitted by their vector, viruses have evolved mechanisms to dampen down immune responses to allow more vigorous viral replication. We are defining the mechanisms by which flaviviruses actively block immune responses in their mosquito vectors. We are also working to understand whether these immune-blocking mechanisms contribute to the ability of flaviviruses to be transmitted by specific mosquito species.
- Do mosquito transposons alter flavivirus transmission?
The genomes of all organisms contain a large amount of ‘junk’ DNA, which has classically been thought not to contribute to cellular functions. However, this view is changing and a particular type of ‘junk’ DNA called a ‘transposon’ has been shown to enhance the ability of mosquitoes to transmit arboviruses. We are investigating how the activation of transposons under different environmental conditions alters the ability of mosquitoes to transmit flaviviruses.
We have innovated a number of research tools and methods that are benefiting researchers worldwide working on Aedes aegypti. These methods include improved standardised cell lines that will increase experimental reproducibility between different research groups; the first CRISPR mutant mosquito cell lines; and methods to study the global proteome derived from transposons.
Our research could uncover new ways of modifying Aedes aegypti to reduce arbovirus transmission, which would reduce human suffering and fatalities associated with the viruses transmitted by this important vector mosquito. There would also be an associated decrease in the negative impacts that large-scale epidemics have on healthcare systems and the economies of affected countries.