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Advancement Of A Personalised Approach To Minimising Infective Complications In Cancer Care
Funder
National Health and Medical Research Council
Funding Amount
$265,138.00
Summary
Managing infections in patients with cancer have become more difficult and unpredictable because of new generation cancer therapies. Measuring the response of the immune system (immune profiling) will allow us to predict which patients will develop infection so that action such as vaccination can be taken to reduce their risk. This program will refine immune profiling to personalise infection care for cancer patients and to introduce it into hospital practice.
Predicting Infections In Cancer Of The Plasma Cells In Bone Marrow (myeloma)
Funder
National Health and Medical Research Council
Funding Amount
$107,764.00
Summary
The study will look for new risks for infection in patients with multiple myeloma, a cancer of plasma cells in the bone marrow. Currently these patients are expected to live longer because of the discovery and use of new generation cancer drugs. By finding new infection risks, the treatment of life threatening infections can be improved or infection can be prevented so patients have a better quality of life whilst on cancer treatment.
The pathogen Cryptococcus neoformans is responsible for hundreds of thousands of deaths annually. If the infection is survived, relapse caused by evolved forms of the original infecting strain is common. Our research has uncovered similar genetic changes in isolates from unrelated patients that implicate epigenetic processes in relapse and reveal potential vulnerabilities of the pathogen. The proposed work is to investigate these changes to assist in our antifungal drug development efforts.
Fungal Determinants And Host Cell Death Signals In Fatal Candida Infections
Funder
National Health and Medical Research Council
Funding Amount
$654,091.00
Summary
Fungal pathogens are a major burden in hospital settings as they evade the immune system and cause lethal sepsis. This project will determine the molecular factors utilized by the fungal pathogen Candida to kill host immune cells. We will investigate whether immune cell death contributes to the high fatality rate, commonly associated with systemic Candida infections, and whether this can be targeted by novel therapeutics.
Acquisition And Transmission Of Respiratory Pathogens In Persons With Cystic Fibrosis (CF): Development And Implementation Of Novel Molecular Tools
Funder
National Health and Medical Research Council
Funding Amount
$155,416.00
Summary
There are a number of significant bacteria that cause infection in children with cystic fibrosis. Early eradication may have a positive impact on clinical outcome. Molecular biology assists in the rapid identification and characterisation of clinical strains of these bacteria. This project will develop molecular biology tools and then use them to pimporve detection of these significant bacteria in early childhood of people with CF.
NLRC5, A New Regulator Of Helicobacter-induced Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$640,136.00
Summary
Helicobacter pylori lives in the stomach of half the world’s population and is a major cause of human disease, including cancer. The body fights H. pylori infection by mobilising white blood cells to the stomach lining, resulting in inflammation. We have evidence that H. pylori can attenuate this inflammation by targeting a host protein, NLRC5. This project will determine the role of NLRC5 in preventing inflammation and cancer due to H. pylori infection.
Establishing The Use Of Bacterial Genomics In Australia
Funder
National Health and Medical Research Council
Funding Amount
$157,669.00
Summary
We propose to establish a set of fully assembled reference genomes through new technologies and methods to analyse data from high throughput genome sequencing of important bacterial pathogens in Australia. We aim to demonstrate the capabilities of genome sequencing in clinical situations by comparing the genomes from clinical bacterial isolates to the established and annotated reference genomes.
Dengue, Zika and Chikungunya are viral diseases transmitted to humans by mosquitoes. Our research uses a naturally-occurring bacteria, Wolbachia, to stop mosquitoes transmitting these viruses to humans. Our proposal addresses critical knowledge gaps in the biology of mosquitoes and Wolbachia to enable large-scale field-deployment optimisation in affected countries. The outcome of our research will immediately translate to disease control efforts in northern Australia, Asia and Latin America.
Novel Antifungal Strategies Using Drug Response Networks
Funder
National Health and Medical Research Council
Funding Amount
$484,420.00
Summary
Fungal cells are quite similar to our own making it hard to find good drug targets. This project aims to enhance current antifungal drugs with agents that interfere with iron, which is needed for fungal growth. We will see how fungal cells change the genes they use when they are treated with drugs alone and combined with molecules that mop up iron. We will then track the pathways within cells that are targets of the affected genes, and find points where these pathways can be blocked.
Fungal Phospholipases: A Novel Drug Discovery Platform
Funder
National Health and Medical Research Council
Funding Amount
$588,679.00
Summary
Invasive fungal infections are a serious and escalating health issue. They cause severe disease with a high death rate and are very costly to the health system. This is especially the case in immunocompromised patients, such as those with blood malignancies, organ transplant recipients and AIDS. The number of currently available drugs for the treatment of fungal infections is limited and they are, in general, either not very effective or toxic. The development of fungal strains resistant to thes ....Invasive fungal infections are a serious and escalating health issue. They cause severe disease with a high death rate and are very costly to the health system. This is especially the case in immunocompromised patients, such as those with blood malignancies, organ transplant recipients and AIDS. The number of currently available drugs for the treatment of fungal infections is limited and they are, in general, either not very effective or toxic. The development of fungal strains resistant to these drugs is also becoming problematic. There is an urgent need to discover and develop new drugs effective against fungal infections through identifying new targets in the fungal cell and-or targets that prevent the spread of infection in the human host. We were the first to describe an enzyme, phospholipase B (PLB1), which is secreted by the medically important fungus, Cryptococcus neoformans, and is important in invasion of human tissue by the fungus. It is also important in remodelling of membranes in the fungal cell. This enzyme is sufficiently different from human phospholipases to be a good target for antifungal drugs. In this project, we aim to synthesise and test molecules which should inhibit the activity of PLB and in this way block its harmful effects. We will test the effects of such drugs to make sure they do not interfere with human enzyme systems. Inhibitory compounds may also be used to kill the fungal cells, especially if administered together with currently used therapies. The design and development of new antifungal drugs with a novel mode of action represents a major advance in the treatment of fungal disease, and a saving of some A$60000 per affected patient (estimated from a recent US study).Read moreRead less