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.
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347223
Funder
Australian Research Council
Funding Amount
$100,000.00
Summary
Quantitative PCR facility for New England region of NSW. The project will deliver the first real-time PCR facility in the New England Region of NSW for use by University, CSIRO and Industry scientists. The facility will be based at the University of New England and be used by animal scientists, molecular biologists, parasitologists, immunologists and botanists at these institutions, in many cases in collaborative research projects. It will also support the training of seven PhD students and a po ....Quantitative PCR facility for New England region of NSW. The project will deliver the first real-time PCR facility in the New England Region of NSW for use by University, CSIRO and Industry scientists. The facility will be based at the University of New England and be used by animal scientists, molecular biologists, parasitologists, immunologists and botanists at these institutions, in many cases in collaborative research projects. It will also support the training of seven PhD students and a post-doctoral fellow. The facility will be unique to the region and will remove our current need to use facilities in Brisbane or Sydney.Read moreRead less
Topical and cryoanaesthesia for livestock husbandry. The livestock industries contribute $15billion annually to Australia's economy, playing a vital role in rural communities. However we must respond to changing demands of our customers, by complementing our competitive disease-free advantage with welfare-conscious production systems. This project will address the threat of growing international demands for improved animal welfare in farming. We will provide research and technical solutions, pro ....Topical and cryoanaesthesia for livestock husbandry. The livestock industries contribute $15billion annually to Australia's economy, playing a vital role in rural communities. However we must respond to changing demands of our customers, by complementing our competitive disease-free advantage with welfare-conscious production systems. This project will address the threat of growing international demands for improved animal welfare in farming. We will provide research and technical solutions, providing pain mangement products for on-farm use that will reduce animal suffering during routine husbandry interventions. The project offers significant benefits for producers by protecting their industries against the threats of a welfare embargo on our livestock products. Read moreRead less