I am a virologist carrying out research to determine the mechanisms underlying rotavirus cellular tropism and the pathogenesis of rotavirus disease. Rotavirus is the major cause of infantile gastroenteritis worldwide. I am combining the expertise of my group in rotavirus biology with the power of inter-disciplinary collaborations in the areas of sugar chemistry, cell biology, structural biology and diabetes to expand understanding in these areas. Novel treatments and improvements in rotavirus va ....I am a virologist carrying out research to determine the mechanisms underlying rotavirus cellular tropism and the pathogenesis of rotavirus disease. Rotavirus is the major cause of infantile gastroenteritis worldwide. I am combining the expertise of my group in rotavirus biology with the power of inter-disciplinary collaborations in the areas of sugar chemistry, cell biology, structural biology and diabetes to expand understanding in these areas. Novel treatments and improvements in rotavirus vaccines are the long term goal of our research.Read moreRead less
Worldwide there are approximately 40 million people living with HIV-AIDS. An effective HIV vaccine does not exist at present. Therefore, current strategies to control the HIV pandemic include the use of life saving antiretroviral drugs. While the current drugs are successful in controlling infections, new and more effective agents are needed that inhibit HIV replication by distinct mechanisms due to the inevitable development of drug resistant strains of HIV. The HIV reverse transcriptase enzyme ....Worldwide there are approximately 40 million people living with HIV-AIDS. An effective HIV vaccine does not exist at present. Therefore, current strategies to control the HIV pandemic include the use of life saving antiretroviral drugs. While the current drugs are successful in controlling infections, new and more effective agents are needed that inhibit HIV replication by distinct mechanisms due to the inevitable development of drug resistant strains of HIV. The HIV reverse transcriptase enzyme is essential for HIV replication and has been a successful target for nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs act in part by stabilizing the reverse transcriptase enzyme, thus blocking enzyme function. However, no drugs have been developed that can specifically prevent formation of the reverse transcriptase enzyme, which would result in the production of noninfectious viral particles. We propose that formation of the active reverse transcriptase enzyme, from a large polyprotein called Gag-Pol, proceeds through a homodimer intermediate, which represents an ideal target for blocking reverse transcriptase formation in HIV infected cells. This homodimer intermediate is an attractive target with greater potential for disruption with small molecule inhibitors compared to the mature reverse transcriptase enzyme as it is less stable than the reverse transcriptase found in viruses. This study will determine whether formation of the active RT enzyme is dependent on this intermediate. In addition, we will examine how the reverse transcriptase encoded on Gag-Pol regulates activation of the HIV protease, which is also critical for the formation of infectious virus particles. These studies will increase our understanding of how the virus produces infectious particles and will identify new approaches for targeting the HIV reverse transcriptase enzyme.Read moreRead less
Understanding How Virus Infection Accelerates Type 1 Diabetes Development
Funder
National Health and Medical Research Council
Funding Amount
$610,774.00
Summary
We linked rotavirus infection in children at-risk of type 1 diabetes with faster diabetes development. A heightened response to the virus is implicated by our mouse model studies. We will determine if more rapid mouse diabetes due to rotavirus requires this heightened response, and if this response is also made by cells from diabetes patients after stimulation with rotavirus or other relevant viruses. These studies are vital to learn how viruses affect type 1 diabetes and devise interventions.
Silent Mutations In The HIV-1 Reverse Transcriptase Selected During Antiretroviral Therapy
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
This project seeks to determine the role of silent mutations in the HIV reverse transcriptase that are selected during drug therapy in HIV infected individuals on HIV fitness, reverse transcriptase function and the emergence of drug resistance. This study will increase our understanding of the mechanisms by which the virus evades the effects of antiretrovirals and will provide a rationale for deciding on the best drug combinations for use in patients infected with specific HIV strains (clades).
Elucidating The Pathogenic Role Of Rotavirus Infection In Type 1 Diabetes Development
Funder
National Health and Medical Research Council
Funding Amount
$535,579.00
Summary
Rotavirus infection is the main cause of severe diarrhoea in children, and has been implicated in accelerated progression of genetically at-risk children towards type 1 diabetes in two independent studies. My group has further discovered that rotavirus also accelerates diabetes onset in mice in a novel immunological process. In this project, we will determine the mechanism behind this disease exacerbation in the mice, to facilitate understanding of the process in children.