Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basi ....Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basis and evolution of this important polymorphism. O-antigens are used for typing Shigella and also elicit strong immunity. The molecular data will help establish DNA based typing and vaccine development.Read moreRead less
Bacterial Proteomics: From Cell Division to Novel Antibiotic Targets. When a cell divides it is essential that each newborn cell gets a complete copy of the DNA. To ensure that this happens, cell division must be tightly controlled. It is not known how this occurs in bacteria. However, if we knew what molecules were involved in this control, we could target them to kill harmful bacteria. This project aims to identify such regulatory molecules as candidate targets for antimicrobial agents, with a ....Bacterial Proteomics: From Cell Division to Novel Antibiotic Targets. When a cell divides it is essential that each newborn cell gets a complete copy of the DNA. To ensure that this happens, cell division must be tightly controlled. It is not known how this occurs in bacteria. However, if we knew what molecules were involved in this control, we could target them to kill harmful bacteria. This project aims to identify such regulatory molecules as candidate targets for antimicrobial agents, with a view to developing powerful, novel antibiotics to protect us from the imminent threat of bioterrorism and antibiotic-resistant bacteria.
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The effect of age on regulatory T cell control of the innate and adaptive antiviral immune responses. Viral pathogens are a lead cause of infant mortality in the world. This project will define how T regulatory cells limit protective antiviral immune responses in the young. This information is critical for the development of potent antiviral vaccines that are effective from the newborn period without inducing autoimmunity. It will also provide novel insight into the way T regulatory cells can b ....The effect of age on regulatory T cell control of the innate and adaptive antiviral immune responses. Viral pathogens are a lead cause of infant mortality in the world. This project will define how T regulatory cells limit protective antiviral immune responses in the young. This information is critical for the development of potent antiviral vaccines that are effective from the newborn period without inducing autoimmunity. It will also provide novel insight into the way T regulatory cells can be manipulated both to dampen immunity, which can be used to develop strategies to reduce immune mediated disease and limit transplant rejection. Read moreRead less
Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarif ....Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarify how malaria parasites evade the host's immune response and help to protect Australia by providing drug targets for the control of this invasive disease.Read moreRead less
Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. ....Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. This detailed information will be used in the education of the public and in debates about evolution. The project will also train at least five students in molecular and evolutionary microbiology, essential for facing future challenges.
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Ross River virus - identification of virulence determinants in clinical isolates from across Australia. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. The project has several national benefits. It will elucida ....Ross River virus - identification of virulence determinants in clinical isolates from across Australia. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. The project has several national benefits. It will elucidate whether there is any association between RRV strain and the severity of human disease. It will also identify viral markers that could assist public health officials in determining likely disease outcomes of outbreaks and could provide new avenues for the design of antiviral strategies.Read moreRead less
Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create compone ....Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create components of the highly complex and poorly characterised cell wall. Since this structure is unique in the bacterial world, we expect to identify and characterise pathways that are unique to mycobacteria.Read moreRead less
New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in ot ....New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in other diseases such as cancer. The outcomes of this project will include advances in malaria drug development that build on Australian drug discovery efforts, seeding further funding opportunities from industry and other sources and contributing research training and capacity building in Australia.Read moreRead less
Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool ....Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool to identify novel bacterial virulence determinants. We anticipate that a greater knowledge of the factors that contribute to the host-pathogen interaction will provide new insights into the subversion of host cell processes by bacterial pathogens of animals, plants and humans.
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Investigating the Ability of Honey to Inhibit Bacterial Biofilms Found in Chronic Wounds. Chronic (non-healing) wounds are a serious health problem in Australia. One quarter of our institutionalized aged population have pressure ulcers. The difficulty in treating these wounds is that most contain communities of bacteria, called biofilms, that are not killed by conventional antibiotics. Special honeys from Australia and NZ that are effective in chronic wound treatment can eradicate these biofilms ....Investigating the Ability of Honey to Inhibit Bacterial Biofilms Found in Chronic Wounds. Chronic (non-healing) wounds are a serious health problem in Australia. One quarter of our institutionalized aged population have pressure ulcers. The difficulty in treating these wounds is that most contain communities of bacteria, called biofilms, that are not killed by conventional antibiotics. Special honeys from Australia and NZ that are effective in chronic wound treatment can eradicate these biofilms. This project will identify the components in honey that do this and determine how they do it, to provide a more effective chronic wound treatment. It will decrease the prevalence of these wounds in Australia and the associated personal trauma and health costs.Read moreRead less