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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
Cellular And Molecular Mechanisms Of Fungal Infection Pathogenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$561,028.00
Summary
Fungal infections are serious problems for patients with depressed immunity such as chemotherapy or transplant patients. More effective antifungal treatments are needed. We will study a model of fungal infection in zebrafish embryos that recapitulates human penicilliosis. The research will study how the infection establishes and how different types of white blood cells either help or hinder infection establishment. The results will point to new approaches for treating serious fungal infections.
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.
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.
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.
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
The Clinical Value Of Serology And Molecular Tests For Diagnosing Invasive Aspergillosis In At-risk Hematology Patients
Funder
National Health and Medical Research Council
Funding Amount
$1,095,500.00
Summary
Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic t ....Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic tests are not good at detecting infection or often only detect the infection at advanced stages when treatment is ineffective. Because of the limitations of current diagnostic tests the current practice is to give empiric antifungal therapy (EAFT) early to treat Invasive Aspergillosis. However studies have demonstrated that this therapy has only resulted in a minor reduction in the mortality rates and it causes significant drug toxicity. It is a suboptimal treatment modality. New tests have been developed to diagnose Invasive Aspergillosis. These tests are for the detection of an Aspergillus protein in blood and for the detection of Aspergillus DNA in the blood. Available data suggests that these new tests are sensitive in the detection of Invasive Aspergillosis. Also other studies suggest that these new tests make an early diagnosis and seem to be able to monitor responses to treatment. However no study has been performed to date which demonstrates that the use of these tests can impact on important patient outcomes. This trial is designed to determine whether the use of the new tests to guide therapy will help improve treatment of Invasive Aspergillosis, reduce drug toxicity and reduce the death rate in the high-risk patients as compared with the current standard method of diagnosis and treatment with EAFT. If the trial is successful then this represents a significant advancement in the treatment and survival of leukaemic and bone marrow transplantation patients.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.
Immuno-metabolic Interactions Of The Fungal Superbug Candida Auris
Funder
National Health and Medical Research Council
Funding Amount
$674,105.00
Summary
Infections threaten hospital patients and undermine our ability to use advanced medical treatments for conditions such as cancer. Candida auris is an emerging superbug causing infections in hospitals and nursing homes that are commonly resistant to front-line antifungal therapy. To build the knowledge foundation for improved treatments, this proposal aims to define how C. auris escapes immune defences and understand the metabolic mechanisms that shape immune responses and infection outcomes.
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.