Molecular determinants of an allergic response. Some humans develop allergies after exposure to environmental allergens while others do not. At present, the reason for this individual variation is not known. By comparing the processes activated in allergic versus non-allergic individuals, this study will identify critical molecules involved in making individuals susceptible to allergies, which will be used to develop safer and more effective allergy vaccines.
Designing effective Gram negative bacterial vaccines. There is a need for the development of novel vaccines for use in animals and humans. This project will to address this need by studying the functions of bacterial 'blebs' as potent inducers of the host immune system and by developing these nano-sized particles for use as safe and cost-effective vaccine candidates.
Investigation of the resilience of immune memory to manipulation by pathogens. Vaccines have a major impact on the wellbeing of humans as well as productivity and welfare of veterinary species and pets. New vaccines have therefore a tremendous effect on both the economy and the community. Here we investigate in how far an adjuvanted vaccine can influence the type of immune response induced during subsequent infection when the pathogen has developed mechanisms to subvert the induced protective im ....Investigation of the resilience of immune memory to manipulation by pathogens. Vaccines have a major impact on the wellbeing of humans as well as productivity and welfare of veterinary species and pets. New vaccines have therefore a tremendous effect on both the economy and the community. Here we investigate in how far an adjuvanted vaccine can influence the type of immune response induced during subsequent infection when the pathogen has developed mechanisms to subvert the induced protective immune response. This question has profound implications for all vaccine and adjuvant development activities, as the resilience of immune memory is not yet considered an important parameter in the design of adjuvants yet it is fundamental to the successful of vaccines against many pathogens.Read moreRead less
A comprehensive analysis of the outer membrane, surface exposed and secreted proteome of Pasteurella multocida. Pasteurella multocida is the causative agent of a range of animal diseases. The molecular mechanisms of P. multocida pathogenesis are poorly understood and the current vaccines generally ineffective. We will identify all P. multocida outer membrane, surface exposed and secreted proteins expressed during natural infection, or under conditions which mimic natural infection, by a global p ....A comprehensive analysis of the outer membrane, surface exposed and secreted proteome of Pasteurella multocida. Pasteurella multocida is the causative agent of a range of animal diseases. The molecular mechanisms of P. multocida pathogenesis are poorly understood and the current vaccines generally ineffective. We will identify all P. multocida outer membrane, surface exposed and secreted proteins expressed during natural infection, or under conditions which mimic natural infection, by a global proteomics approach. We believe that secreted proteins and those found on the outer surface of the bacterial cell are likely to be crucial virulence determinants. The expected outcomes are the identification of a number of candidate vaccine antigens and an enhanced understanding of Pasteurella pathogenesis.Read moreRead less
Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the ....Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the proposed project will develop a novel efficient, safe and notably biodegradable self-adjuvanting delivery system that can be fully customised to match an antigen of choice. This foundational research should provide important advances for commercial immune stimulatory applications.Read moreRead less
Immune-imprinting nanoparticles (iNPs). This research promises new classes of immune-imprinting, biodegradable nanoparticles (iNPs) with anti-inflammatory properties. The engineering of such particles requires fundamental understanding of their properties that enable specific cellular interactions to regulate immunity with new anti-inflammatory pathways. For pulmonary delivery, spray-dried amino acid microspheres with tailored surfaces as carriers can be generated using the innovative microfluid ....Immune-imprinting nanoparticles (iNPs). This research promises new classes of immune-imprinting, biodegradable nanoparticles (iNPs) with anti-inflammatory properties. The engineering of such particles requires fundamental understanding of their properties that enable specific cellular interactions to regulate immunity with new anti-inflammatory pathways. For pulmonary delivery, spray-dried amino acid microspheres with tailored surfaces as carriers can be generated using the innovative microfluidic drying approach. The potential applications of iNPs are wide-ranging and are not restricted to pulmonary targeting. The potential commercial implications for Australia's emerging biopharmaceutical industry are substantial.Read moreRead less
Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.Read moreRead less
Recombinant probiotics for prevention of enteric infections in piglets. Shigatoxigenic and enterotoxigenic strains of Escherichia coli cause severe diarrhoeal disease and oedema disease in piglets. The resultant morbidity and mortality is a major cause of financial loss to the pig industry both in Australia and overseas. We have conceived a highly novel approach to prevention of these diseases involving molecular mimicry of host receptors for the E. coli toxins and adhesins on the surface of a ....Recombinant probiotics for prevention of enteric infections in piglets. Shigatoxigenic and enterotoxigenic strains of Escherichia coli cause severe diarrhoeal disease and oedema disease in piglets. The resultant morbidity and mortality is a major cause of financial loss to the pig industry both in Australia and overseas. We have conceived a highly novel approach to prevention of these diseases involving molecular mimicry of host receptors for the E. coli toxins and adhesins on the surface of a harmless bacterium. Oral administration of this agent to piglets has the potential to bind free toxins in the gut and prevent colonization of the intestines by the pathogens, thereby preventing disease.Read moreRead less
Structural and functional alteration of red blood cells by Babesia parasites. Cattle Tick Fever caused by Babesia parasites causes significant economic loss to the Australian livestock industry. New approaches to prevent this disease are urgently needed but this requires greater knowledge of how the parasites cause disease in cattle. By identifying novel proteins involved in the disease process we will be able to make better vaccines and drugs and save the Australian livestock industry millions ....Structural and functional alteration of red blood cells by Babesia parasites. Cattle Tick Fever caused by Babesia parasites causes significant economic loss to the Australian livestock industry. New approaches to prevent this disease are urgently needed but this requires greater knowledge of how the parasites cause disease in cattle. By identifying novel proteins involved in the disease process we will be able to make better vaccines and drugs and save the Australian livestock industry millions of dollars each year.Read moreRead less
Functional genomics of large clostridial plasmids. The aims of this genomics project are to determine how large DNA elements called plasmids are able to be transferred between different strains of a bacterium that causes disease in domestic livestock. These plasmids carry genes that encode the potent protein toxins that are responsible for several diseases. To understand how these diseases are spread we must learn how the plasmids have evolved and whether they can move from bacterium to bacteriu ....Functional genomics of large clostridial plasmids. The aims of this genomics project are to determine how large DNA elements called plasmids are able to be transferred between different strains of a bacterium that causes disease in domestic livestock. These plasmids carry genes that encode the potent protein toxins that are responsible for several diseases. To understand how these diseases are spread we must learn how the plasmids have evolved and whether they can move from bacterium to bacterium. The successful completion of the project will result in a detailed understanding of genetic elements that are important mediators of several diseases of importance to Australian primary industry.Read moreRead less