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
Investigating The Interface Between Host Innate Immune Cells And A Fungal Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$578,085.00
Summary
Fungi which infect humans are a major health problem, especially 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 a pathway that we have shown is required for growth inside host cells. This knowledge will open new avenues for treatment.
The Role Of Fatty Acid Metabolism In Pathogenicity.
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Fungi which infect humans are a major health problem, especially for those with compromised immune systems (eg. AIDS, transplant and cancer patients). Pathogenic fungi must evade the host s immune system whilst deriving nutrients for growth. Some fungi evade the immune system by residing within host cells. This poses significant challenges to growth due to the nutrient poor environment. By understanding how these fungi adapt to growth inside host cells, new avenues for treatment will emerge.
Molecular Mechanisms Of Intracellular Growth, Survival And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$335,816.00
Summary
Fungi which infect humans are a major health problem, especially 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 a pathway that we have shown is required for growth inside host cells. This knowledge will open new avenues for treatment.
Identification Of Telomere-specific Recombination Pathways
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Human cells stop to grow when the natural ends of chromosomes become too short. One way of how cancer cells evade this growth arrest is by using a copy-mechanism to extend short chromosome ends. Ironically, this copy mechanism is usually used by cells to keep the structure of chromosomes intact in order to prevent mutations that cause cancer. Here we will study a novel protein that contributes to the copy mechanism at short chromosome ends, but not as much in normal mutation prevention.
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
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.
Phylogeny As A Basis For Molecular Identification Of Pathogenic Fungi
Funder
National Health and Medical Research Council
Funding Amount
$440,750.00
Summary
Pathogenic fungi are becoming increasingly important in causing potentially life-threatening diseases in immunocompromised hosts (e.g. AIDS, transplant patients). Many of the emerging fungal pathogens are inherently resistent to triazole antifungal drugs and clinical responses to established drugs remain suboptimal, despite apparent sensitivity in the laboratory. Current techniques of fungal identification are insensitive, unspecific, slow, labour-intensive and require skilled personnel for the ....Pathogenic fungi are becoming increasingly important in causing potentially life-threatening diseases in immunocompromised hosts (e.g. AIDS, transplant patients). Many of the emerging fungal pathogens are inherently resistent to triazole antifungal drugs and clinical responses to established drugs remain suboptimal, despite apparent sensitivity in the laboratory. Current techniques of fungal identification are insensitive, unspecific, slow, labour-intensive and require skilled personnel for the ID of less common fungi. To improve clinical outcomes by prompt selection-initiation of the best antifungal regimes, and to truncate the interval from initiation of therapy to cure, early, accurate identification of the causative agent is crucial, making a fast identification to the species level after culture or direct from clinical specimens a necessity. A correct fungal identification can only be achieved if the phylogenetic relationships between the pathogenic organisms and their taxonomy is resolved. Gene detection is more reproducible than detection of morphological and biochemical differences. The proposal focuses on the establishment of an accurate phylogenetic system of pathogenic fungi, which will form the basis of a universally applicable molecular identification system and to develop a molecular reference database for human pathogenic fungi. This project will contribute sequence data of pathogenic fungi to the Tree of Life project. This project unites expertise in classical mycology, molecular biology, bioinformatics and infectious diseases, to develop an accurate phylogeny of medically important fungi, providing a unique opportunity to establish a quality controlled reference database accessible via the world-wide-web. This will provide a faster and more accurate ID of pathogenic fungi, which will lead to better clinical treatment.Read moreRead less
Transposable Element Mobility And Chromosomal Rearrangement In The Fungal Pathogen Cryptococcus During Human Infection
Funder
National Health and Medical Research Council
Funding Amount
$322,028.00
Summary
Pathogenic fungi present in the environment have emerged as an increasingly common threat to human health. Cryptococcus neoformans and the closely related species Cryptococcus gattii are the leading causes of life-threatening fungal meningitis, and Australia is one of the few countries where both species are prevalent. Although C. neoformans is an increasingly common cause of infection in immunocompromised patients such as those suffering from AIDS, approximately one in four infected individuals ....Pathogenic fungi present in the environment have emerged as an increasingly common threat to human health. Cryptococcus neoformans and the closely related species Cryptococcus gattii are the leading causes of life-threatening fungal meningitis, and Australia is one of the few countries where both species are prevalent. Although C. neoformans is an increasingly common cause of infection in immunocompromised patients such as those suffering from AIDS, approximately one in four infected individuals has no apparent immune system defect. For patients with AIDS, in the absence of antiretroviral therapy cryptococcal infection is incurable and requires lifelong treatment with antifungal medication to keep the infection in check. During infection, Cryptococcus is under tremendous stress enforced not only by the immune system and the presence of antifungals, but also by the high temperature, nutrient limiting environment encountered in the host. The proposed research will reveal how Cryptococcus evolves in this environment to enable persistence of infection despite medical intervention. I propose that naturally occurring mobile genetic elements present in the Cryptococcus genome cause chromosomal rearrangements during long term infection to produce gene deletions and duplications that facilitate survival. By characterising these changes and the genes associated with them, the research will identify novel genes involved in pathogenesis and will increase our understanding of the infection process. The expected outcome of this project is a detailed understanding of the roles mobile element movement and chromosomal rearrangement play in Cryptococcus during infection, and how these affect genes that contribute to the pathogenic process. The fundamental knowledge gained from this study will facilitate studies designed to combat infections in the clinical setting, provide new drug targets and help foster the development of more effective therapies.Read moreRead less