Maintaining fidelity in viral Ribonucleic acid (RNA) polymerases. This project will provide informed insights into the dynamics of viruses that currently impact a healthy start to life, ageing well and productively, and preventative healthcare. The analysis of viruses that cause gastroenteritis outbreaks will increase our understanding of how these viruses replicate and spread.
The biosynthesis of structural proteins in parasites. The socio-economic impact of parasitic diseases, in Australia and throughout the world, is enormous- they kill 2-3 million people per year and cost livestock industries billions of dollars per annum. Some are serious food and waterborne threats, such as the coccidia, because they are transmitted from person-to-person via the faecal-oral route, or via ingestion of contaminated water or food, or through the ingestion of cysts in raw or underco ....The biosynthesis of structural proteins in parasites. The socio-economic impact of parasitic diseases, in Australia and throughout the world, is enormous- they kill 2-3 million people per year and cost livestock industries billions of dollars per annum. Some are serious food and waterborne threats, such as the coccidia, because they are transmitted from person-to-person via the faecal-oral route, or via ingestion of contaminated water or food, or through the ingestion of cysts in raw or undercooked meat. They cause diarrhoea, which in some cases, can be life-threatening. We will understand how the coccidia protect themselves as they move from host to host and, through that understanding, develop new ways to control them and eliminate the suffering caused by parasitic diseases.Read moreRead less
CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the ....CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the age that an individual first encounters the infection. Our project will identify critical periods in life that direct T cell programming to subsequent protective or destructive responses, providing new insights into the developing immune system that may be exploited to treat disease or develop vaccines.Read moreRead less
The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in ....The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in order to study latent infection at the cellular level, and within infected monkeys. This will provide the first insights into the dynamics of latency - how these cells are produced and die - and should lead to novel approaches to controlling chronic infection.Read moreRead less
Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and r ....Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and research skill base. Young scientists will be trained in state-of-the-art research techniques in a cross-disciplinary environment that is the way of future biological research. The project may identify potential drug targets for malaria or other infectious diseases. The Intellectual Property will be protected and commercialised.Read moreRead less
Parasite virulence: the role of activation and suppression of P2X7 receptors. Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. L ....Parasite virulence: the role of activation and suppression of P2X7 receptors. Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. Leishmaniasis, recently found in Australia, is a risk for overseas travellers, livestock and wildlife. This research will provide an understanding of what makes these parasites successful, paving the way for development of novel drugs to combat these chronic diseases.Read moreRead less
Bacterial filamentation as a survival strategy: a goldmine for the discovery of new cell division regulators. The increasing emergence of untreatable bacterial infections is a serious threat to the health of Australians. Medical advances (organ transplants, chemotherapy), increases in diabetes, and an aging population increase the risk of infections caused by bacteria that are now resistant to most available antibiotics. New classes of antibiotics are urgently needed to treat these infections. T ....Bacterial filamentation as a survival strategy: a goldmine for the discovery of new cell division regulators. The increasing emergence of untreatable bacterial infections is a serious threat to the health of Australians. Medical advances (organ transplants, chemotherapy), increases in diabetes, and an aging population increase the risk of infections caused by bacteria that are now resistant to most available antibiotics. New classes of antibiotics are urgently needed to treat these infections. This project uses a novel approach to identify the mechanisms bacterial cells use to control their growth and avoid attack by our immune system. The research will identify potential targets for the development of new, effective antibiotics to kill multi-resistant bacteria, and ensure Australia's position at the forefront of infection control.Read moreRead less
Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also p ....Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also provides the source material for exploitation of bacterial products such as antibiotics. The results from understanding a complete set of mutational changes through genomic analysis will provide the most direct estimates of variation in evolving bacteria.Read moreRead less
Anthocyanin Inhibitors to the Influenza Virus. The increasing resistance of circulating influenza strains to current anti-viral inhibitors has prompted an investigation to screen, design, synthesize and evaluate a new class of natural product based inhibitors to the virus employing novel and innovative mass spectrometry, computational and structural approaches. Preliminary studies reveal they offer benefits in terms of a different mode of binding to influenza neuraminidase, remote from many know ....Anthocyanin Inhibitors to the Influenza Virus. The increasing resistance of circulating influenza strains to current anti-viral inhibitors has prompted an investigation to screen, design, synthesize and evaluate a new class of natural product based inhibitors to the virus employing novel and innovative mass spectrometry, computational and structural approaches. Preliminary studies reveal they offer benefits in terms of a different mode of binding to influenza neuraminidase, remote from many known resistance mutations, and may have specific practicality against N1 neuraminidase in H1N1 and H5N1 viruses responsible for all pandemics of the 20th and 21st centuries. The research will enable the potential of these inhibitors to be fully assessed at the molecular level for the first time.Read moreRead less
Treating tuberculosis: targeted delivery of multidrug nano-suspensions. Tuberculosis (TB) is a lung disease of worldwide prevalence. Treatment times are long and mortality is high in children and the elderly. Current treatments are ineffective and drug resistant TB is a real pandemic threat. The project will develop a cost-effective nano-particle system that can be incorporated into conventional nebulisers for use worldwide.