1. Antiviral drug resistance: Using both seasonal human influenza viruses and viruses of pandemic potential, such as highly pathogenic A(H5N1), we are interested in the mutations that arise under selection pressure of different influenza antivirals, how readily they arise and their effect on susceptibility and viral function.
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2. Novel influenza antivirals: We are interested in working with licensed influenza antivirals, as well as those in late phase clinical trials around the world. Currently these include projects related to four neuraminidase inhibitors: oseltamivir, zanamivir, peramivir and laninamivir; a polymerase inhibitor, favipiravir (T-705); and nitzoxanide.a repurposed drug with anti-influenza activity.
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3. Use of in vivo models: We use a ferret infection model to asses various aspects of antiviral drug effectiveness, optimal treatment strategies and the effect of resistance mutations on viral replication and transmissibility.
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1. Avian influenza surveillance of wild birds: Together with collaborators we conduct surveillance of wild birds for avian influenza viruses throughout Australia and even conduct surveillance of penguins in Antarctica! Detection, molecular and functional analysis of strains leads to better understanding of the evolution and ecology of avian influenza viruses.
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2. In vivo transmissibility of avian and swine influenza viruses: Using the ferret model we can better understand the pathogenicity, replication kinetics and transmissibility of avian or swine influenza viruses. Such information is important to predict the risk that these animal influenza viruses pose to humans and their likelihood for sustained human-to-human spread.
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We currently have projects available for Honours, Masters or PhD students. Please contact Aeron Hurt at aeron.hurt@influenzacentre.org if you would like to find out more about these projects.

The influenza antiviral drug, oseltamivir (Tamiflu), is widely prescribed and has been stockpiled by many countries, including Australia, for use in a future pandemic to treat influenza infection. However, in recent years the effectiveness of the drug has been hotly debated. Sole reliance on this class of antivirals (neuraminidase inhibitor) means that there is an urgent need to characterise the effectiveness of other antivirals for influenza. This project will incorporate both in vitro and in vivo techniques to study the effect of different antivirals on viral replication, pathogenesis, transmission and drug resistance. In vitro techniques involve real-time PCR, Sanger sequencing, cell culture based inhibition assay and viral growth kinetics studies. For in vivo assessment, an established ferret model of influenza infection will be used to determine the effectiveness of different treatment strategies. Immunological and metabolomics assessment involving RNA sequencing and metabolomics analysis will be used to further elicit the mechanism of how the antivirals ameliorate influenza infection.

• Molecular biology: reverse genetics; site-directed mutagenesis; cloning; pyrosequencing and Sanger sequencing
• Classical virology and functional techniques: cell culture; virus culture; plaquing; TCID₅₀; haemagglutination-inhibition; neuraminidase inhibition assays
• Ferret models of influenza infection: intranasal, intratrachael and intraocular infection; nasal washes; antiviral drug administration; morbidity measurements

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