Molecular basis of attenuation in live Mycoplasma vaccines. This proposal aims to use an innovative approach to address an urgent issue raised by the end users of an Australian-owned poultry vaccine with an extensive global market. Recently multiple mutations have been detected in the vaccine re-isolated from vaccinated birds in the field around the world. We will apply a combination of a novel technique for targeted mutagenesis, genome sequencing, and animal experimentations, to address the sig ....Molecular basis of attenuation in live Mycoplasma vaccines. This proposal aims to use an innovative approach to address an urgent issue raised by the end users of an Australian-owned poultry vaccine with an extensive global market. Recently multiple mutations have been detected in the vaccine re-isolated from vaccinated birds in the field around the world. We will apply a combination of a novel technique for targeted mutagenesis, genome sequencing, and animal experimentations, to address the significance of these mutations. Results will improve our understanding of the basis of attenuation of the vaccine, its mechanism of action, and provide commercial confidence in the safety of the vaccine, which is needed to support Australian Universities and Businesses, and the global poultry industry.Read moreRead less
Developing feasible in situ control of mange disease in wombats. Our goal is the development of feasible in situ control of sarcoptic mange in wombat populations. Globally important, the Sarcoptes scabiei mite infects >100 mammal species and is among the 50 most common human diseases, causing health, welfare and population impacts. This infection is treatable, and we will test a new treatment (fluralaner), develop new models to guide management, and conduct replicated field trials. This will ena ....Developing feasible in situ control of mange disease in wombats. Our goal is the development of feasible in situ control of sarcoptic mange in wombat populations. Globally important, the Sarcoptes scabiei mite infects >100 mammal species and is among the 50 most common human diseases, causing health, welfare and population impacts. This infection is treatable, and we will test a new treatment (fluralaner), develop new models to guide management, and conduct replicated field trials. This will enable science-based guidelines, advancing disease control, local eradication, and regulatory approval for wombats. Our research framework is adaptable to other mange-impacted species, and advance methods and theory for control of treatable disease in wildlife.Read moreRead less
Treating Equine Laminitis. This project aims to explore the causes of equine laminitis, and to work with a newly-established Australian biopharma company to develop the world's first anti-laminitis medication. Equine laminitis is a painful, crippling disease of the foot, often necessitating euthanasia, and is the second-most common cause of death in domestic horses. In 2007, a landmark study identified insulin toxicity as a primary cause of laminitis, and subsequent research has identified over- ....Treating Equine Laminitis. This project aims to explore the causes of equine laminitis, and to work with a newly-established Australian biopharma company to develop the world's first anti-laminitis medication. Equine laminitis is a painful, crippling disease of the foot, often necessitating euthanasia, and is the second-most common cause of death in domestic horses. In 2007, a landmark study identified insulin toxicity as a primary cause of laminitis, and subsequent research has identified over-stimulation of the IGF-1 receptor as the most likely mechanism. This project aims to prove that mechanism and to develop an effective treatment.Read moreRead less
Characterisation of insulin-independent glucose uptake mediated by guanine nucleotide-binding proteins (G-proteins) coupled receptors. This project will provide first class postdoctoral training for Dr Sato in the laboratory of A/Prof Bengtsson one of the pioneers in the field of cell metabolism. He will learn new approaches to the study of cell signalling including the use of ribonucleic acid interference (RNAi) technologies and of a series of functionally altered mutants of phosphatidylinosito ....Characterisation of insulin-independent glucose uptake mediated by guanine nucleotide-binding proteins (G-proteins) coupled receptors. This project will provide first class postdoctoral training for Dr Sato in the laboratory of A/Prof Bengtsson one of the pioneers in the field of cell metabolism. He will learn new approaches to the study of cell signalling including the use of ribonucleic acid interference (RNAi) technologies and of a series of functionally altered mutants of phosphatidylinositol (PI) 3-kinase that he will bring back to Monash University. A better understanding of the cell signalling mechanisms involved in glucose transport will be of enormous benefit in developing new approaches to the treatment of diseases such as type II diabetes.Read moreRead less
Improving diagnostic accuracy and treatment options for equine PPID. Equine Pituitary Pars Intermedia Dysfunction (PPID) is a common, chronic and potentially life-threatening disease of older horses and ponies. Although a treatment is available, the disease is poorly understood and there are some concerns that the current diagnostic technology is not delivering accurate results. Thus, this project aims to develop a more accurate diagnostic test for PPID, while exploring the relationship between ....Improving diagnostic accuracy and treatment options for equine PPID. Equine Pituitary Pars Intermedia Dysfunction (PPID) is a common, chronic and potentially life-threatening disease of older horses and ponies. Although a treatment is available, the disease is poorly understood and there are some concerns that the current diagnostic technology is not delivering accurate results. Thus, this project aims to develop a more accurate diagnostic test for PPID, while exploring the relationship between PPID and metabolic syndrome, to generate new insights into the cause and consequences of both diseases. As an added benefit, the project will assist horseracing laboratories to improve their detection methods for peptide doping in younger competition horses.
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Linking immunomodulation and latency in alphaherpesvirus infection. Herpesviruses cause major diseases in humans and all domestic animal species. Latency forms a significant part of the evolutionary success of herpesviruses, by enabling transmission of the virus throughout the lifetime of the host. Our work has shown that an alphaherpesvirus protein can divert the host’s immune response to become more antibody-mediated and less T cell-mediated. This study explores the consequences of this immune ....Linking immunomodulation and latency in alphaherpesvirus infection. Herpesviruses cause major diseases in humans and all domestic animal species. Latency forms a significant part of the evolutionary success of herpesviruses, by enabling transmission of the virus throughout the lifetime of the host. Our work has shown that an alphaherpesvirus protein can divert the host’s immune response to become more antibody-mediated and less T cell-mediated. This study explores the consequences of this immune diversion, and examines whether this reduced T cell response enables the development of latent infections. Disrupting the virus-host balance by alterations to this conserved viral protein will enable novel approaches to controlling these economically significant viruses.Read moreRead less
Imperfect vaccination drives herpesvirus evolution through recombination. Vaccines are used to help control disease caused by herpesviruses in animals, but some vaccination programs may drive the evolution and spread of herpesviruses with increased fitness (transmissibility, replication and virulence) through recombination. This project aims to study an important avian herpesvirus (infectious laryngotracheitis virus) in the natural host (poultry) to gain fundamental knowledge of how vaccination ....Imperfect vaccination drives herpesvirus evolution through recombination. Vaccines are used to help control disease caused by herpesviruses in animals, but some vaccination programs may drive the evolution and spread of herpesviruses with increased fitness (transmissibility, replication and virulence) through recombination. This project aims to study an important avian herpesvirus (infectious laryngotracheitis virus) in the natural host (poultry) to gain fundamental knowledge of how vaccination programs influence the emergence of diverse recombinant viruses, and identify which types of vaccination programs are best at preventing the emergence of fitter and more virulent viruses. The results are expected to inform vaccination practices to allow more effective control of these viruses in poultry and other animals.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100735
Funder
Australian Research Council
Funding Amount
$395,204.00
Summary
Understanding infectious laryngotracheitis virus recombination. This project will study the factors that lead to recombination between strains of infectious laryngotracheitis virus (ILTV) concomitant with increased virulence. In previous studies of ILTV, two new genotypes of virulent field strains were shown to be independent recombinants derived from distinct attenuated ILTV commercial vaccines. These strains became the dominant field viruses responsible for widespread and severe disease outbre ....Understanding infectious laryngotracheitis virus recombination. This project will study the factors that lead to recombination between strains of infectious laryngotracheitis virus (ILTV) concomitant with increased virulence. In previous studies of ILTV, two new genotypes of virulent field strains were shown to be independent recombinants derived from distinct attenuated ILTV commercial vaccines. These strains became the dominant field viruses responsible for widespread and severe disease outbreaks in Australian poultry flocks. This project will enhance understanding of the conditions that led to these deleterious natural recombination events and enable the industry to avoid the emergence of new virulent field strains in the future. 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
Discovery Early Career Researcher Award - Grant ID: DE210101063
Funder
Australian Research Council
Funding Amount
$462,948.00
Summary
Bacterial cell invasion factors as vaccine targets. This project aims to determine the virulence factors responsible for cellular invasion and systemic spread of Mycoplasma bovis, and use genome editing technologies (CRISPR-Cas9) to create gene knock out mutants that cannot invade host cells and test their potential as vaccine candidates in animals. Mycoplasma bovis is an emerging cause of mastitis, the most important infectious disease in the dairy industry, and causes significant economic loss ....Bacterial cell invasion factors as vaccine targets. This project aims to determine the virulence factors responsible for cellular invasion and systemic spread of Mycoplasma bovis, and use genome editing technologies (CRISPR-Cas9) to create gene knock out mutants that cannot invade host cells and test their potential as vaccine candidates in animals. Mycoplasma bovis is an emerging cause of mastitis, the most important infectious disease in the dairy industry, and causes significant economic losses. The vaccine candidates developed in this project are expected to be used to control outbreaks of mastitis, and to improve biosecurity, production and animal welfare in the Australian and global dairy industries.Read moreRead less