Study level

  • Master of Philosophy

Faculty/School

Faculty of Health

School of Biomedical Sciences

Topic status

We're looking for students to study this topic.

Research centre

Supervisors

Associate Professor Francesca Frentiu
Position
Associate Professor
Division / Faculty
Faculty of Health

External supervisors

  • Dr Leon Hugo, QIMR Berghofer
  • Assoc Prof David Harrich, QIMR Berghofer

Overview

Dengue is a major mosquito-borne disease affecting 390 million people annually across 100 countries. Disease results from infection with dengue viruses, which are single positive-stranded RNA viruses in the family Flaviviridae. Defective interfering particles (DIPs) are virus-like particles with greatly reduced genomes that are byproducts of RNA virus replication and replicate only in the presence of standard virus (Vignuzzi and Lopez 2019, doi: 10.1038/s41564-019-0465-y). DIPs occur naturally during Dengue infection (Li et al. 2011, doi: 10.1371/journal.pone.0019447) and suppress DENV replication in cell culture (Wang et al. 2020, doi: 10.1021/acsinfecdis.9b00384).

This project will evaluate the potential for a synthetic DIP to interrupt the transmission of dengue virus to the primary mosquito vector Aedes aegypti. Hypotheses of this project are that DIPs suppress DENV infection in mosquitoes and reduce viraemia in vertebrate hosts to below the threshold needed to infect mosquitoes.

Approaches

This project will include mosquito virus challenge experiments, in which mosquitoes are fed on varying ratios of the DIP and DENV in blood meals via an artificial membrane feeding apparatus or fed on DIP-treated mice. Viruses will be detected from the mosquitoes after a period of incubation to determine virus titres and the antiviral efficacy of the DIPs. Research will take place within insectaries at QIMR Berghofer utilizing purpose-built facilities and equipment, including constant temperature insect rearing rooms and arbovirus infection laboratories. Skills gained during this project will include tissue culture techniques, methods to quantify virus in vitro by RT-qPCR, TCID50 and other assays, mosquito skills and data analysis.

Outcomes

The project aim is to evaluate the ability of synthetic DIPs to interrupt the DENV transmission cycle through suppression of infection in mosquitoes.Expected outcomes include the generation of robust data on the effect of DIPs on DENV infection and transmission for publication.

Keywords

Contact

For more information contact Dr Leon Hugo at the Mosquito Control Laborator, QIQIMR Berghofer Medical Research Institute by: