Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to prod ....Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to produce lead-like compounds that inhibit the protein's function and may provide novel drug candidates for further development. Furthermore the role of human host cell-associated carbohydrates in parainfluenza infection will be better understood.Read moreRead less
Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produce ....Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produced and may also benefit from advances in our understanding of this elusive virus resulting from the project.Read moreRead less
Noncoding RNAs of insect-specific flaviviruses: biogenesis and functions. This project aims to investigate noncoding RNAs (sfRNAs) of insect-specific flaviruses (ISFs). These RNAs are produced from viral RNA by host ribonuclease and play important role in pathogenesis and transmission of vertebrate-infecting flaviviruses (VIFs). The team has shown that ISFs also produce sfRNAs although likely employing a different mechanism. The project expects to generate new knowledge on ISF sfRNA biogenesis a ....Noncoding RNAs of insect-specific flaviviruses: biogenesis and functions. This project aims to investigate noncoding RNAs (sfRNAs) of insect-specific flaviruses (ISFs). These RNAs are produced from viral RNA by host ribonuclease and play important role in pathogenesis and transmission of vertebrate-infecting flaviviruses (VIFs). The team has shown that ISFs also produce sfRNAs although likely employing a different mechanism. The project expects to generate new knowledge on ISF sfRNA biogenesis and functions using combination of modern structural, biochemical, and innovative molecular virology methods. The outcome will be a clearer understanding of processes governing flavivirus host restriction and evolution. This will improve understanding of virus-host interactions and train students in cutting edge techniques.Read moreRead less
Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be diff ....Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be difficult for public health officials to detect WNV if it is introduced to Australia. In this project we aim to develop more accurate laboratory tests to detect infections with the deadly, exotic WNV using new strategies. Read moreRead less
Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrho ....Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrhoeagenic E. coli serotypes. A direct outcome of this will be improved human health, as E. coli O157:H7 can cause life threatening infections in humans. The study will also examine the contribution of specific adhesins to biofilm formation; measures to prevent biofilm formation may reduce the persistence and spread of E. coli O157:H7 in the environment.Read moreRead less
Hyperactive endogenous retroviruses and their impact on the koala genome. Koala populations are in steep decline with the ubiquitous koala retrovirus (KoRV) strongly linked with disease. KoRV and other less studied endogenous retrovirus (ERVs) are extremely active within the genome of koalas to a level never observed in any other vertebrate genome. This study will map ERV integration sites within koalas from across their geographic range country and use long-read genomics approaches to understan ....Hyperactive endogenous retroviruses and their impact on the koala genome. Koala populations are in steep decline with the ubiquitous koala retrovirus (KoRV) strongly linked with disease. KoRV and other less studied endogenous retrovirus (ERVs) are extremely active within the genome of koalas to a level never observed in any other vertebrate genome. This study will map ERV integration sites within koalas from across their geographic range country and use long-read genomics approaches to understand the link between KoRV and other ERVs, the impact on koala caused by dramatic genomic rewiring, and the mechanisms of genomic immunity which supress ERV activity and mitigate disease. Findings will provide insights into the ongoing arms race between virus and host and inform conservation of an iconic species.Read moreRead less
Understanding the mechanism of Wolbachia-mediated antiviral protection. Insects are involved in the transmission of many viral diseases of both plants and animals. A considerable number of these diseases have adverse effects for public health or cause large economic losses in agriculture. We were the first to discover that a common bacteria protects insects from virus infection. Knowledge of the mechanisms used by the bacteria to interfere with virus accumulation will facilitate novel strategies ....Understanding the mechanism of Wolbachia-mediated antiviral protection. Insects are involved in the transmission of many viral diseases of both plants and animals. A considerable number of these diseases have adverse effects for public health or cause large economic losses in agriculture. We were the first to discover that a common bacteria protects insects from virus infection. Knowledge of the mechanisms used by the bacteria to interfere with virus accumulation will facilitate novel strategies for control of virus disease. The findings of this project will enable Australian researchers and industry to design innovative approaches to control diseases that are transmitted by insects.Read moreRead less
What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dy ....What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dying from viruses; however, it is not known what is cause and effect. This project will clarify Varroa’s exact role in the evolution of virulence in RNA viruses. The intended outcome is increased knowledge allowing the design of an effective treatment to prevent the death of honeybee colonies.Read moreRead less
Fighting disease on farms: how do vaccinations drive evolution of new pathogen strains? Vaccinating against some types of infectious diseases can drive evolution of new variants of the pathogen. This project will show how bacterial populations evolve in response to vaccination in farms, leading to new vaccination strategies and improved vaccine formulations to better control diseases that are caused by highly variable bacteria.