The main purpose of this study is to understand how airborne fungi affect asthmatics who are allergic to them. Fungi or moulds release large numbers of spores into the air that are inhaled. In many cases fungal spores outnumber other particles that carry allergen, such as pollens or cat dander, by 100 to 1. This makes fungi the most common potential allergen in the environment. Fungi have been associated with respiratory diseases including fungal sinusitis, asthma, rhinitis, allergic alveolitis ....The main purpose of this study is to understand how airborne fungi affect asthmatics who are allergic to them. Fungi or moulds release large numbers of spores into the air that are inhaled. In many cases fungal spores outnumber other particles that carry allergen, such as pollens or cat dander, by 100 to 1. This makes fungi the most common potential allergen in the environment. Fungi have been associated with respiratory diseases including fungal sinusitis, asthma, rhinitis, allergic alveolitis and sick building syndrome. Largely due to their diversity and complexity, allergenic fungi have not been well studied and the ways in which individuals vary when inhaling spores is not known. Unlike other allergenic particles, it is unlikely that fungal spores release their allergen as soon as they are inhaled because we have shown in earlier in vitro studies that fungi continue to release allergen over time and this is likely to be the case when they are inhaled. Our laboratory has developed two new techniques that allow us to measure how many spores people inhale and whether they are allergic to them. This study will use these tools to detect and identify the important allergenic fungi involved in domestic and outdoor exposure of asthmatics, the degree of contribution to the total allergen load to which subjects are exposed and identify in what conditions fungi are the causal agents in location-specific symptoms. This study will also investigate allergen production of fungi in situ in the human nose, which will have application in allergic sinusitis and asthma amongst other respiratory diseases. We will investigate how readily allergenic spores germinate in the nose and under what conditions they release allergen.Read moreRead less
Identifying And Characterising The Molecular Determinants Of Fungal Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$315,375.00
Summary
Fungi which infect humans represent one of the fastest growing public health problems. Like bacteria, fungi can pose a serious threat to infected individuals. This is especially true for individuals whose immune system is compromised in any way due to the direct action of another disease such as AIDS, treaments for diseases like cancer or treatment to prevent rejection in organ transplants. The problem is compounded by the lack of safe and effective treament for fungal infections. Many pathogeni ....Fungi which infect humans represent one of the fastest growing public health problems. Like bacteria, fungi can pose a serious threat to infected individuals. This is especially true for individuals whose immune system is compromised in any way due to the direct action of another disease such as AIDS, treaments for diseases like cancer or treatment to prevent rejection in organ transplants. The problem is compounded by the lack of safe and effective treament for fungal infections. Many pathogenic fungi are capable of growing in two very different forms. Usually only one of these forms is pathogenic and causes disease. Therefore, the genes which keep the fungus in the pathogenic form are important factors for infection. By understanding how fungi are capable of infection and avoiding the immune system, good practices and treatments can be development for these life threatening infections.Read moreRead less
The fungal pathogen Cryptococcus neoformans is responsible for up to a million deaths annually, necessitating the development of novel antifungals. We have characterised the GTP biosynthesis enzyme IMP dehydrogenase, revealing it is critical for infection, and structural and functional analysis reveals routes to inhibitor specificity. In the proposed work will develop novel antifungal compounds that target this enzyme, as well as investigate related enzymes as potential future drug targets.
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.
Dissecting Virulence Attributes In A Human Pathogenic Fungus
Funder
National Health and Medical Research Council
Funding Amount
$814,596.00
Summary
Fungi that infect humans are a major health problem worldwide, particularly for those with compromised immune systems (eg. AIDS, transplant and cancer patients). These fungi cause disease by evading the immune system whilst deriving nutrients for growth. Some fungi evade the immune system by residing within host cells; a hostile and nutrient poor environment. This project will study genes that are required for growth inside host cells. This knowledge will open new avenues for treatment.
Elucidation Of Proteins Expressed By Pathogenic Fungi During Animal Infection
Funder
National Health and Medical Research Council
Funding Amount
$558,267.00
Summary
Fungi cause a diverse range of diseases and are very difficult to treat. This project looks at the proteins that are made by infectious fungi while they are causing disease in animal cells. Proteins made in particularly high abundance may be essential for the fungus to live and grow in animal tissues. By specifically targeting their production, it should be possible to stop the infection without harming the host cell.
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.
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.
Is The Excess Mortality Amongst Tuberculosis Survivors Explained By Chronic Pulmonary Aspergillosis? Investigating Burden, Diagnosis, And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Chronic pulmonary aspergillosis (CPA) is a serious lung infection due to the mould Aspergillus. It affects people with damaged lungs, such as those who have had tuberculosis. In Vietnam, TB is extremely common, and there should be many cases of CPA. However, because diagnostic facilities are poor, CPA is often wrongly labelled as failed TB treatment, and patients receive the wrong therapy. My research will determine the size of the problem in Vietnam and how best to address it.