Research Projects
Our research activities encompass a broad range of areas, including mechanisms of influenza transmissibility, antiviral resistance, immune response and fundamental biology. We use several different methodologies, including molecular biology, animal models and population studies.

Early recognition and response to influenza infection
This research focuses on the role of the innate immune system following influenza infection. In particular, we are interested in understanding and characterising airway immune cells and soluble factors that act as a first line of defence. Current studies have focused on soluble and membrane-associated C-type lectins and the role that they play in early recognition and response to influenza virus. Approaches used include modification of host- and virus-encoded factors, mouse and ferret models of infection and in vitro studies using cells and tissues derived from mice, ferrets and humans.

Effect of novel amino acid mutations on the susceptibility of influenza viruses to neuraminidase inhibitors
Novel mutations are introduced into the influenza virus using reverse genetics and site directed mutagenesis. The role of the mutation on neuraminidase inhibitor susceptibility, enzyme activity and virus growth (both in vitro and in vivo) is then assessed. Laboratory based data are compared with structural modelling analyses to better understand the role of key mutations.
Collaborators: Jessica Holien and Michael Parker, St Vincent's Institute of Medical Research, Melbourne

Competitive mixtures model in ferrets to understand the fitness and transmissibility of influenza viruses
To assess the within-host fitness and transmissibility of different influenza viruses, two strains are mixed and used to co-infect a series of ferrets. The relative mixture proportion of those viruses are monitored daily and the are analysed using mathematical models to determine the relative fitness cost of one virus compared with another. The model has been applied to determining the fitness of neuraminidase inhibitor resistant viruses and new antigenic variants.
Collaborators: James McCaw and Jodie McVernon, Vaccine and Immunisation Research Group, Melbourne School of Population Health, The University of Melbourne

Effectiveness of oseltamivir for the treatment of ferrets infected with pandemic and highly pathogenic influenza viruses
A ferret model has been established to investigate the effectiveness of oseltamivir treatment or prophylaxis in reducing infectivity, transmissibility and growth of different viruses. To investigate the impact of different treatment strategies, ferrets are dosed with different concentrations of drug at various time intervals either pre- or post- exposure to the virus. Virological, symptomatic and immunological variables are measured.
Collaborators: Deborah Middleton and Sue Lowther, Australian Animal Health Laboratories

Cross-reactive immunity in a ferret model of influenza
This project assesses the impact of past exposure(s) to influenza virus infection to protect against subsequent challenges with influenza viruses of the same and different subtypes. We are developing tools to directly measure early and late immune responses in ferrets after infection with human influenza viruses or vaccination. This information is used to interpret how the immune response acts to protect ferrets from subsequent challenge with influenza viruses, and how to enhance this response to protect against newly emerging influenza strains.
Collaborators: Jenny Mosse, School of Applied Sciences and Engineering, Monash University Gippsland; Heath Kelly, Epidemiology Unit, VIDRL; Steve Rockman, CSL Limited; Katherine Kedzierska, Department of Microbiology and Immunology, The University of Melbourne; Jodie McVernon, Vaccine & Immunisation Research Group, Melbourne School of Population Health, The University of Melbourne

Top of page

Serological analysis for A(H1N1)pdm infection and vaccine coverage
A number of serosurveys are being conducted throughout Australia to ascertain the infection rates of A(H1N1) Pandemic virus in 2009 and 2010. Antibodies generated after infection or vaccination are used as a proxy measure of infection. We have assessed several patient and community collections around Australia to determine the proportion of people infected with the newly emergent virus or vaccinated with the A(H1N1) Pandemic vaccine. Research also focuses on the ability of patients of various disease status to respond to currently available A(H1N1) Pandemic vaccines.
Collaborators: Wolfram Haller, Department of Gastroenterology & Clinical Nutrition, The Royal Children’s Hospital; Gary Dowse, Communicable Disease Control Directorate Department of Health Western Australia; James Trauer, Department of Health Northern Territory; Peter Markey, Centre of Disease Control Northern Territory; Katherine Kedzierska, Department of Microbiology and Immunology, The University of Melbourne; Jodie McVernon, Vaccine & Immunisation Research Group, Melbourne School of Population Health, The University of Melbourne

Molecular evolution of influenza viruses
We analyse the genetic and antigenic properties of circulating influenza viruses to track how they change over time and location. Our interests include evolutionary patterns that manifest in phylogenetic lineages and geographic regions, as well as the evolutionary behaviour of different viral types and subtypes.
Collaborators: Gavin Smith, Duke-NUS Graduate Medical School, Singapore; Derek Smith and Colin Russell, Cambridge University UK

The ecology of animal influenza viruses in Australia
Studies are ongoing to collect and analyse specimens taken from wild birds in Australia for the presence of avian influenza viruses. Experiments are also undertaken to optimise sample collection, handling and methodology to improve the isolation rate of viruses. Studies are also being conducted study the genetic variability in equine influenza viruses taken from the outbreak in Australia in 2007.
Collaborators: Peter Kirkland and Edla Arzey, NSW Department of Primary Industries; Simone Warner, Victoria Department of Primary Industries

Top of page

NHMRC Program: Understanding and controlling influenza
The Centre is a participant in a National Health and Medical Research Council Program Grant (2010 – 2014). The Program has two broad goals: to understand fundamental mechanisms that establish maximum effective cellular immunity to influenza A viruses and to build the foundations for clinical application of strategies to induce cellular immunity to these viruses. These goals are being addressed through a range of collaborative projects between the chief investigators and team members at the Department of Microbiology and Immunology at the University of Melbourne (UM), the WHO Collaborating Centre, the Ludwig Institute, the School of Population Health (UM) and the CSIRO Australian Animal Health Laboratory.
Chief Investigators: Peter Doherty (UM), David Jackson (UM), Anne Kelso (WHO Collaborating Centre), Weisan Chen (Ludwig Institute for Cancer Research), Stephen Turner (UM), Lorena Brown (UM)

Epigenetic regulation of cytotoxic T lymphocyte function
This project investigates the epigenetic regulation of the critical co-receptor CD8 on CD8⁺ T lymphocytes, which are important mediators of cellular immunity to influenza virus infection through their ability to kill infected cells. The responsiveness of these lymphocytes can be heritably modulated by up- and down-regulating surface CD8 levels with the cytokines interferon-γ and interleukin-4, respectively. Work to date suggests that IL-4 regulation of CD8 is associated with altered CpG methylation of the CD8α gene. Together with other Program research on the regulation of genes involved in cytotoxicity, it is hoped that these studies will identify the molecular mechanisms that underlie the acquisition and heritability of cytotoxic T lymphocyte functions in viral immunity.
Collaborators: Stephen Turner and Brendan Russ, Department of Microbiology and Immunology, University of Melbourne

Top of page

Collaborative Agreements with Industry
The Centre is a party to two collaborative research and development agreements with industry bodies. All such agreements are reviewed by the Australian Government Advisory Committee to ensure that they have the potential to advance public health, have scientific merit and adhere to principles of neutrality, transparency, independence and accountability.

Cooperative Research and Development Agreement with the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) (2008–2011)
This project aims to enhance the number and geographic range of influenza vaccine viruses isolated in eggs as candidates for commercial influenza vaccine manufacture.

Cooperative Research and Development Agreement with Novartis Vaccines & Diagnostics (Marburg, Germany): Development and provision of influenza virus strains isolated on MDCK 33016PF cells for vaccine production (2008–2011)
In this project, the Centre is evaluating the suitability of a proprietary Novartis cell line (MDCK 33016PF) for influenza virus isolation and growth as a basis for cell-based vaccine manufacture.

Top of page