)
Laboratory Head
Associate Professor Gilda Tachedjian, BSc (Hons), PhD
Staff
Senior Burnet Fellow: Dr Secondo Sonza, BSc (Hons), PhD
Senior Research Officer: Dr Jenny Anderson BSc (Hons), PhD
Research Assistants
David Tyssen, BAppSc Biotech
Katie Moore, BSc (Hons)
Adam Johnson, BSc(Hons)
Sushama Telwatte, BMedSc (Hons)
Tasnim Zakir, BSc (Hons)
Students
Johanna Wapling, BSc (Hons)
Soo Huey Yap, BSc (Hons)
Jennifer La, BMedChem(Hons)
Collaborators
Associate Professor Nicolas Sluis-Cremer, Department of Medicine, University of Pittsburgh, USA
Associate Professor P. Richard Harrigan, British Columbia Centre of Excellence, Vancouver, British Columbia, Canada
Professor Thomas Hope, Dept Cell and Molecular Biology, Northwestern University, Chicago, IL, USA.
Dr Jeremy Paull, Starpharma Holdings Ltd, Baker Heart Research Building, Melbourne, Vic, Australia
Professor Richard Cone, Dept of Biophysics, Johns Hopkins University, Baltimore, MD.
Dr Tom Moench, ReProtect, Baltimore, MD.
Professor David Fairlie, Institute for Molecular Biosciences, The University of Queensland, QLD, Australia
Dr David Chalmers, Monash University Faculty of Pharmacy and Pharmaceutical Sciences, Parkville, Vic, Australia
Dr Martin Scanlon, Monash University Faculty of Pharmacy and Pharmaceutical Sciences, Parkville,
Vic, Australia
Dr David Rhodes, AVEXA, Richmond, Vic, Australia
Associate Professor Mibel Aguilar, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic, Australia
Associate Professor Patrick Perlmutter, School of Chemistry, Monash University, Clayton, Australia
Dr Julian Elliot, Infectious Diseases Unit, TheAlfred hospital
Professor C. Martin Stoltzfus, Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Dr Damian Purcell, Department Microbiology and Immunology, University of Melbourne
Dr Andreas Suhrbier, Queensland Institute of Medical Research, Brisbane
Professor Suzanne Crowe, Burnet Institute
Associate Professor Paul Gorry, Burnet Institute
Associate Professor Johnson Mak, Burnet Institute
Dr Melissa Churchill, HIV Neuropathogenesis Laboratory, Burnet Institute
Research Overview
The Molecular Interactions Group (MIG) was established in 2003 and studies interactions between viral proteins and host cell factors that are critical for HIV replication in order to understand fundamental aspects of virus replication and to develop novel agents for the treatment and prevention of HIV/AIDS.
The group’s work primarily focuses on the HIV-1 reverse transcriptase and understanding how modulation of the protein:protein interactions between the two subunits of this enzyme affect reverse trancriptase function and HIV replication. Our basic research findings have led to translational studies to develop small molecules and peptidomimetics that target reverse transcriptase and inhibit its function.
We also studying the role of host cell factors that are required for HIV replication and examining the role of the host cell restriction factor, APOBEC3, on HIV-1 replication.
Our laboratory studies the role of novel mutations in the HIV-1 RT, including those found in the C-terminal domain of the RT, in conferring decreased susceptibility to antiretroviral drugs and their role in virological failure. These studies have the potential to improve genotyping assays for the prediction of drug resistance in HIV infected patients that are used by clinicians to guide antiretroviral therapy.
In addition, the sexual transmission of HIV is the major source of infection in developing countries.We are currently developing topical microbicides based on either synthetic or innate factors that can be used by women to prevent the sexual transmission of HIV and other STIs.
Research Objectives
To understand the role of HIV reverse transcriptase dimerization on enzyme function and HIV replication.
To define the role of the reverse transcriptase domain in HIV maturation. To develop novel inhibitors of the HIV reverse transcriptase.
To understand the role of mutations in the connection domain of the HIV reverse transcritpase on drug resistance and virological failure.
To understand the role of host cell factors that are required for HIV replication.
To understand the role of APOBEC3G host cell factors restricting early HIV replication.
To develop topical microbicides that prevent the sexual transmission of HIV and STIs.
Research Highlights
• Demonstration that potent members of a class of HIV-1 drugs called nonnucleoside reverse transcriptase inhibitors inhibit the production of viral particles by increasing the processing of viral polyproteins inside the host cell. Our findings represent the first example of a small molecule that can block the late stages of HIV-1 replication by this mechanism and provides proof of concept for the pursuit of novel drugs that can target this process.
• Discovery of a region at the HIV-1 reverse transcriptase dimer interface that is essential for reverse transcriptase dimer formation and function.
• Discovery of a novel mutation in the reverse transcriptase that is selected in HIV-1 infected patients receiving antiretroviral therapy that confers resistance to zidovudine and nevirapine. These findings have potential implications for improving genotyping algorithms used to predict drug resistance in HIV-1 infected individuals