Development of a proto-type vaccine against gastrointestinal nematode larvae. Gastrointestinal parasites are the major cause of production losses in the Australian sheep and wool industries. Drug treatment is predominantly used to control infections but drug resistance has reached critical levels and is threatening the viability of sheep production in many rural areas. In collaboration with an international Animal Health company, we aim to develop vaccines against these parasites and provide a c ....Development of a proto-type vaccine against gastrointestinal nematode larvae. Gastrointestinal parasites are the major cause of production losses in the Australian sheep and wool industries. Drug treatment is predominantly used to control infections but drug resistance has reached critical levels and is threatening the viability of sheep production in many rural areas. In collaboration with an international Animal Health company, we aim to develop vaccines against these parasites and provide a clean, non-toxic alternative to drug treatment. The groundbreaking research involved in this project will also keep Australian animal scientists at the forefront of vaccine research and increase their capacity to attract further support from Industry.Read moreRead less
Pathogenesis, regulation and genomics of the ovine footrot pathogen, Dichelobacter nodosus. Footrot is one of the most economically significant diseases of sheep in Australia. The aim of this project is to develop a detailed understanding of how the bacterium that causes this infection is able to infect the sheep hoof and result in clinical disease. The complete sequence of the genome of the causative bacterium will be determined, enabling us to deduce its genetic potential. The completed projec ....Pathogenesis, regulation and genomics of the ovine footrot pathogen, Dichelobacter nodosus. Footrot is one of the most economically significant diseases of sheep in Australia. The aim of this project is to develop a detailed understanding of how the bacterium that causes this infection is able to infect the sheep hoof and result in clinical disease. The complete sequence of the genome of the causative bacterium will be determined, enabling us to deduce its genetic potential. The completed project will significantly advance fundamental knowledge of the disease process and will lead to the development of improved methods for the control of the disease, with concomitant cost savings to Australian primary industry.Read moreRead less
Avoiding the immune response: lessons from 'simple' bacteria. Some of the most important bacterial diseases of domestic animals are caused by mycoplasmas. Improved control of these diseases would significantly improve agricultural productivity by reducing losses associated with reduced feed conversion efficiency and increased susceptibility to other diseases, as well as improve animal welfare and public health, by reducing the need for antibiotic therapy to control these diseases in food produci ....Avoiding the immune response: lessons from 'simple' bacteria. Some of the most important bacterial diseases of domestic animals are caused by mycoplasmas. Improved control of these diseases would significantly improve agricultural productivity by reducing losses associated with reduced feed conversion efficiency and increased susceptibility to other diseases, as well as improve animal welfare and public health, by reducing the need for antibiotic therapy to control these diseases in food producing animals.Read moreRead less
STRUCTURAL CHARACTERIZATION OF ACTIVE CONSTITUENTS IN PLANT EXTRACTS WITH POTENTIAL FOR THE CONTROL OF OVINE LICE AND PARASITIC WORMS. The control of lice and parasitic worms are two of the major problems currently confronting the Australian sheep industry. Several plant extracts utilized in traditional medicine have shown a remarkable efficacy in the control of these pests in humans. This project will investigate the sheep lousicidal and anthelmintic activity of a number of plants, and identif ....STRUCTURAL CHARACTERIZATION OF ACTIVE CONSTITUENTS IN PLANT EXTRACTS WITH POTENTIAL FOR THE CONTROL OF OVINE LICE AND PARASITIC WORMS. The control of lice and parasitic worms are two of the major problems currently confronting the Australian sheep industry. Several plant extracts utilized in traditional medicine have shown a remarkable efficacy in the control of these pests in humans. This project will investigate the sheep lousicidal and anthelmintic activity of a number of plants, and identify and chemically characterize the active constituents. This research will lead to the production of more environmentally friendly pest control methods and overcome problems of insecticidal resistance currently facing the industry.Read moreRead less
The routes of infection with sheep scrapie and agents that cause related prion diseases. We will define the routes by which the infective agents for scrapie, a debilitating disease of sheep, reach the nervous system after being consumed with food. Scrapie is from the same disease group (prion diseases) as mad cow disease. There would be a large economic cost were prion diseases to infect agricultural animals in Australia, through bioterrorism or accident. An outbreak in sheep could ruin the indu ....The routes of infection with sheep scrapie and agents that cause related prion diseases. We will define the routes by which the infective agents for scrapie, a debilitating disease of sheep, reach the nervous system after being consumed with food. Scrapie is from the same disease group (prion diseases) as mad cow disease. There would be a large economic cost were prion diseases to infect agricultural animals in Australia, through bioterrorism or accident. An outbreak in sheep could ruin the industry, as our export markets would be immediately blocked, and thousands of animals would be killed to stop disease spread. The benefit of clearly understanding how the infective agents reach the nervous system is that this may lead to strategies to intervene, and thus limit the spread and seriousness of infection.Read moreRead less
The Molecular Basis of Copper Metabolism in Sheep. The unusual copper metabolism of sheep represents a significant agricultural problem. They are very susceptible to copper deficiency, but readily accumulate copper to toxic levels in the liver leading to fatal liver failure. We propose to elucidate the reason for the copper accumulation phenotype of sheep. We are focussing on WND, a copper transporter responsible for copper excretion into bile. We discovered a novel form of sheep WND designated ....The Molecular Basis of Copper Metabolism in Sheep. The unusual copper metabolism of sheep represents a significant agricultural problem. They are very susceptible to copper deficiency, but readily accumulate copper to toxic levels in the liver leading to fatal liver failure. We propose to elucidate the reason for the copper accumulation phenotype of sheep. We are focussing on WND, a copper transporter responsible for copper excretion into bile. We discovered a novel form of sheep WND designated WNDb to distinguish it from the normal form, WNDa. The experiments outlined are designed to understand the function of both proteins in the sheep and their role in copper sequestration.Read moreRead less
Investigation of the immunological properties of a novel adjuvant in sheep. The induction of strong immune responses without side effects is a highly desirable goal in vaccine R&D. The recently developed adjuvant DCtag utilises unique properties of dendritic cells to boost both cellular and humoral immune responses without tissue damage. This project will identify the mechanisms of immune induction of DCtag using unique properties of our sheep cannulation model. This will allow further optimisat ....Investigation of the immunological properties of a novel adjuvant in sheep. The induction of strong immune responses without side effects is a highly desirable goal in vaccine R&D. The recently developed adjuvant DCtag utilises unique properties of dendritic cells to boost both cellular and humoral immune responses without tissue damage. This project will identify the mechanisms of immune induction of DCtag using unique properties of our sheep cannulation model. This will allow further optimisation of DCtag adjuvanticity in sheep, which will then be applied to the delivery of a prototype peptide based vaccine against foot and mouth disease virus, a veterinary disease of global importance, hereby increasing Australia's leadership in biotechnology.Read moreRead less
Application of DNA vaccination to the control of gastrointestinal nematodes in livestock. Gastrointestinal nematode parasites inflict great losses in sheep and cattle and reliance on anthelmintic drugs for their control is problematic. Vaccination would provide a better alternative but has been difficult to achieve. This proposal aims to apply novel DNA vaccination strategies to the development of parasite vaccines through optimisation of DNA delivery, development of new vaccination vectors and ....Application of DNA vaccination to the control of gastrointestinal nematodes in livestock. Gastrointestinal nematode parasites inflict great losses in sheep and cattle and reliance on anthelmintic drugs for their control is problematic. Vaccination would provide a better alternative but has been difficult to achieve. This proposal aims to apply novel DNA vaccination strategies to the development of parasite vaccines through optimisation of DNA delivery, development of new vaccination vectors and modulation of immune responses by co-delivery of cytokine genes. The results of these studies will not only add a new approach to vaccine development against gastrointestinal parasites but will also contribute to our knowledge of DNA vaccination in large animals.Read moreRead less
Application of in vivo electroporation to DNA immunisation. The in vivo delivery of plasmid DNA induces immune responses to the encoded protein vaccine. In large animals including humans, DNA vaccination needs to be further improved before becoming a commercial reality, at least partially due to the very low levels of expression in vivo. In vivo electroporation has proven to be an effective way to enhance the level of protein expression and increase DNA vaccine efficacy. We combine enhanced in ....Application of in vivo electroporation to DNA immunisation. The in vivo delivery of plasmid DNA induces immune responses to the encoded protein vaccine. In large animals including humans, DNA vaccination needs to be further improved before becoming a commercial reality, at least partially due to the very low levels of expression in vivo. In vivo electroporation has proven to be an effective way to enhance the level of protein expression and increase DNA vaccine efficacy. We combine enhanced in vivo expression using electroporation with the co-delivery of plasmids encoding cytokines to enhance and modulate DNA vaccine in sheep. We will apply our findings to bovine viral diarrhoea virus (BVDV), both as an animal model for humans and as an economically important diseases of livestock.Read moreRead less
A proteomic approach to the identification of novel targets for allergy treatment. Eosinophils are involved in parasite immunity and in the pathology of allergic diseases including asthma. Eosinophil recruitment and activation is critical to their functional activity, but the relevant molecular mechanisms have not been fully elucidated. In the present proposal, a unique resource of eosinophils, at different stages of recruitment and activation, will be used for detailed proteomic analysis to ide ....A proteomic approach to the identification of novel targets for allergy treatment. Eosinophils are involved in parasite immunity and in the pathology of allergic diseases including asthma. Eosinophil recruitment and activation is critical to their functional activity, but the relevant molecular mechanisms have not been fully elucidated. In the present proposal, a unique resource of eosinophils, at different stages of recruitment and activation, will be used for detailed proteomic analysis to identify molecules and molecular pathways involved in eosinophil migration and activation. These studies may lead to novel anti-inflammatory strategies and more targeted drug treatments that will generate significant intellectual property and be of enormous benefit to allergy patients worldwide.Read moreRead less