Transport and innate immune properties of DNA in bacterial nano-sized vesicles. All types of living organisms release nano-sized membrane vesicles or “blebs” which they use for intercellular communication and transport of molecules. This project will determine how bacteria package DNA within these vesicles, how this DNA is transported into host cells and how it triggers immune responses in these cells.
Characterization of metabolic networks in a microbial pathogen. New methods are needed to understand complex cellular processes such as metabolism. This proposal will support the development of methods in metabolite profiling and flux analysis that provide a global view of metabolic networks in cells and complement other profiling approaches, such as proteomics and transcriptomics. The development of these approaches (collectively termed Systems Biology) is essential for maintaining Australia sc ....Characterization of metabolic networks in a microbial pathogen. New methods are needed to understand complex cellular processes such as metabolism. This proposal will support the development of methods in metabolite profiling and flux analysis that provide a global view of metabolic networks in cells and complement other profiling approaches, such as proteomics and transcriptomics. The development of these approaches (collectively termed Systems Biology) is essential for maintaining Australia science at the forefront of international efforts (National Research Priority 3; Breakthrough science). This project will also directly contribute to our understanding of metabolism of an important human pathogen and provide training to young Australian scientists.Read moreRead less
Evolution of AB5 toxins. The proposed research program, using the combination of structural biology and cellular biology will provide insight into the evolution of AB5 toxins. This study will not only improve our fundamental understanding how pathogens evolve to invade hosts but could lead to the rational design of antimicrobials. The knowledge gained will increase Australia's international research profile.
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
The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be importan ....The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be important for developing new control strategies for diseases of global significance such as malaria or toxoplasmosis, as well as those of national importance to the food industry of Australia, including diseases like babesiosis and coccidiosis that cause significant economic loss to the livestock and poultry industries each year.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
An Investigation of the Structure and Conformational Stability of a Membrane Associating Protein and its Petidic Ligands. The genome of the parasite most commonly responsible for fatal malaria will be completed this year. Structural elucidations of proteins identified from these genomic data will expedite the identification and classification of proteins synthesised by the parasite that might be developed as vaccines or as targets for anti-malarial therapeutics. In this work, recent developmen ....An Investigation of the Structure and Conformational Stability of a Membrane Associating Protein and its Petidic Ligands. The genome of the parasite most commonly responsible for fatal malaria will be completed this year. Structural elucidations of proteins identified from these genomic data will expedite the identification and classification of proteins synthesised by the parasite that might be developed as vaccines or as targets for anti-malarial therapeutics. In this work, recent developments in structural biology will be employed to obtain the structure of a vaccine candidate and to identify environmental factors that influence the stability of this structure. A novel approach will be taken to determine the conformation of ligands bound to such proteins, which will provide a basis for the development of therapeutics.Read moreRead less
Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned ....Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned about the development of these parasites. The expected outcomes are an understanding of the mechanisms of sexual differentiation and a functional characterisation of novel sex-specific molecules. This will provide significant benefits, such as pivotal prerequisites for new approaches to parasite intervention.Read moreRead less
Identification of the basic elements of Plasmodium transcription. This Discovery Project falls under the NRP for safeguarding Australia. Australian troops stationed in malaria endemic areas face the threat of infection and require medical attention upon return.Any research on malaria will expand our knowledge on prevention and treatment. Australia near malariaendemic locations such as Indonesia and Papua New Guinea.These countries do not have the means to support effective basic research into ....Identification of the basic elements of Plasmodium transcription. This Discovery Project falls under the NRP for safeguarding Australia. Australian troops stationed in malaria endemic areas face the threat of infection and require medical attention upon return.Any research on malaria will expand our knowledge on prevention and treatment. Australia near malariaendemic locations such as Indonesia and Papua New Guinea.These countries do not have the means to support effective basic research into the disease and wealthier countries such as Australia have the responsibility to fill this void.Furthermore, the aims of this Discovery Project are unique within the Australian malaria research community and the results fully complement other studies on transcription regulation of antigenic genes. Read moreRead less
The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-spe ....The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-specific enteropathogenic E. coli and the closely related bacterium, Citrobacter rodentium, which specifically infect rabbits and mice respectively, to investigate the molecular basis of host specificity.Read moreRead less