Targeting Fungal Phospholipid Metabolism For Antifungal Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$828,557.00
Summary
Invasive fungal infections are a serious and escalating health problem. They cause severe disease with a high death rate and are very costly to the health system. New antifungal drugs with novel properties are needed now because there are problems with current drugs. This project aims to develop potent new antifungal drugs that are effective in many fungal diseases and are well-tolerated.
Regulation Of Secretion Of The Fungal Virulence Determinant, Phospholipase B
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted ....Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted by the disease-causing fungus, Cryptococcus neoformans, and that it is important in enabling the fungus to invade the host's cells and spread around the body from the lungs to the brain, where it can cause meningoencephalitis. PLB is also produced by other disease-causing fungi. The mechanism of PLB secretion is completely unknown. In this project we aim to determine the pathways involved in PLB secretion with the intention of exploiting steps unique to pathogenic fungi, for the future design of new anti-fungal drugs.Read moreRead less
Invasive fungal infections are a serious, escalating health issue. They cause severe disease with high death rates and are very costly to the health system. Current drugs often have suboptimal efficacy and cause side effects. New drugs are needed urgently. Many fungi, including the AIDS-related pathogen, Cryptococcus neoformans, secrete phospholipase B (Plbp) to facilitate infection. We will identify and investigate the Plbp secretion pathway as a novel anti-fungal drug target.
Cryptococcal Meningoencephalitis - Fungal Determinants Of Invasion Of The CNS
Funder
National Health and Medical Research Council
Funding Amount
$587,634.00
Summary
Meningitis and brain infection (meningoencephalitis) due to the fungus Cryptococcus, affect over 1 million patients with AIDS annually, especially in developing countries; with more than 600,000 deaths. It is not known how Cryptococci cross from the blood stream into the brain; this must be elucidated in order to prevent and/or control this devastating infection. This project will determine how cryptococci influence host blood cells to act as “Trojan horses” and/or release products that initiate ....Meningitis and brain infection (meningoencephalitis) due to the fungus Cryptococcus, affect over 1 million patients with AIDS annually, especially in developing countries; with more than 600,000 deaths. It is not known how Cryptococci cross from the blood stream into the brain; this must be elucidated in order to prevent and/or control this devastating infection. This project will determine how cryptococci influence host blood cells to act as “Trojan horses” and/or release products that initiate invasion of brain tissue and meningitis.Read moreRead less
Defining domains within Mycoplasma hyopneumoniae surface proteins that interact with host extracellular matrix: efficacy testing of candidate vaccines in swine. Over 90% of Australian commercial pig production facilities are affected by Mycoplasma hyopneumoniae, the causative agent of swine enzootic pneumonia. This disease causes economic losses in Australia of over $20 million per annum and up to $1 billion per annum in major swine rearing countries worldwide. This project will determine the p ....Defining domains within Mycoplasma hyopneumoniae surface proteins that interact with host extracellular matrix: efficacy testing of candidate vaccines in swine. Over 90% of Australian commercial pig production facilities are affected by Mycoplasma hyopneumoniae, the causative agent of swine enzootic pneumonia. This disease causes economic losses in Australia of over $20 million per annum and up to $1 billion per annum in major swine rearing countries worldwide. This project will determine the protective efficacy of new generation vaccines against M. hyopneumoniae, which aim to block the colonisation process and prevent disease .Read moreRead less
Identification and characterisation of Mycoplasma hyopneumoniae surface-molecules that interact with the host epithelium. Mycoplasma hyponeumoniae causes porcine enzootic pneumonia, a disease that significantly impacts swine production. Current vaccines are unable to prevent colonisation of the respiratory tract and are costly to produce and administer. The expression of microbial adhesins that mediate adherence to the extracellular matrix is considered the initial step in host colonisation for ....Identification and characterisation of Mycoplasma hyopneumoniae surface-molecules that interact with the host epithelium. Mycoplasma hyponeumoniae causes porcine enzootic pneumonia, a disease that significantly impacts swine production. Current vaccines are unable to prevent colonisation of the respiratory tract and are costly to produce and administer. The expression of microbial adhesins that mediate adherence to the extracellular matrix is considered the initial step in host colonisation for many bacterial pathogens. We propose to identify M. hyopneumoniae cell surface moleculaes that interact with components of the extracellular matrix. Targetting these cell surface molecules will lead to therapeutics that prevent disease and block colonisation, eventually eradicating the host pathogen from pig production facilities.Read moreRead less
Signalling Pathways And Fungal Virulence – The Inositol Polyphosphate Kinase Pathway In Cryptococcus Neoformans
Funder
National Health and Medical Research Council
Funding Amount
$545,189.00
Summary
Bloodstream fungal infections kill millions of people per year world-wide and are costly to treat. A potentially fruitful strategy for developing new, urgently-needed drugs to fight these infections, is to target signalling pathways, which in fungi, are essential for establishing infection. This proposal investigates how one such pathway, the inositolpolyphosphate kinase pathway, allows fungi to establish infection and will determine which components are suitable targets for drug development.
Discovery Early Career Researcher Award - Grant ID: DE200101832
Funder
Australian Research Council
Funding Amount
$425,941.00
Summary
Mechanisms of immune protection for infectious laryngotracheitis virus. This project aims to investigate the mechanisms of immune protection against infectious laryngotracheitis virus. This will be achieved by investigating the role of local and systemic immunity and the immune cells associated with long-term protection against disease. The mechanisms of protection against this virus remain unknown which impairs the development of efficacious vaccines. Expected outcomes of this project are a mor ....Mechanisms of immune protection for infectious laryngotracheitis virus. This project aims to investigate the mechanisms of immune protection against infectious laryngotracheitis virus. This will be achieved by investigating the role of local and systemic immunity and the immune cells associated with long-term protection against disease. The mechanisms of protection against this virus remain unknown which impairs the development of efficacious vaccines. Expected outcomes of this project are a more rational approach to vaccination resulting in the generation of more effective and safer vaccination strategies that should benefit our important poultry industry. Additionally, the new methodologies and knowledge on mucosal immune markers could be utilised for the study of other pathogens.Read moreRead less
New antiparasitics to protect Australian livestock. There is an urgent need for new antiparasitics to treat multi-drug resistant livestock infections. This project aims to explore the bacteria and fungi present in the microbiomes of heavily infected sheep faeces and pastures, challenging them with environmental cues, including those from associated parasites, to stimulate production of defensive chemicals hidden deep within their genomes. Enabled by an integrated pipeline of high throughput anal ....New antiparasitics to protect Australian livestock. There is an urgent need for new antiparasitics to treat multi-drug resistant livestock infections. This project aims to explore the bacteria and fungi present in the microbiomes of heavily infected sheep faeces and pastures, challenging them with environmental cues, including those from associated parasites, to stimulate production of defensive chemicals hidden deep within their genomes. Enabled by an integrated pipeline of high throughput analytical cultivation, molecular networking, and chemical and biological analyses, expected outcomes include an enhanced ability to explore and exploit valuable chemistry hidden within microbial genomes, leading to the discovery of new classes of natural antiparasitic to safeguard livestock.
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Optimisation of a novel hybrid vaccine for liver fluke disease in cattle. Optimisation of a novel hybrid vaccine for liver fluke disease in cattle. This project aims to optimise the formulation of novel fluke vaccine antigens by constructing combination hybrid recombinant antigens and using a protein adjuvant to improve immunogenicity, and test new antigens expressed in young flukes as vaccines and evaluate their ability to synergise with hybrid vaccines. Fasciola (fluke) infections cause seriou ....Optimisation of a novel hybrid vaccine for liver fluke disease in cattle. Optimisation of a novel hybrid vaccine for liver fluke disease in cattle. This project aims to optimise the formulation of novel fluke vaccine antigens by constructing combination hybrid recombinant antigens and using a protein adjuvant to improve immunogenicity, and test new antigens expressed in young flukes as vaccines and evaluate their ability to synergise with hybrid vaccines. Fasciola (fluke) infections cause serious economic losses to livestock production and fluke drug resistance threatens control, so new therapies such as a vaccine are needed. These vaccines should be evaluated in cattle trials. The major outcome plan is validation of hybrid antigens for commercial vaccine development for fluke control in cattle, leading to more sustainable beef and milk production in Australia.Read moreRead less