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.
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.
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
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.
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
Characterizing The Molecular Mechanisms Of Clinically Important Bacterial-fungal Interactions; The Potential To Uncover Novel Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$480,492.00
Summary
In hospitals and in nature, diverse microbes, such as bacteria and fungi, often live in close proximity to each other. Their interactions can either be helpful or detrimental to one another, and such interactions are likely important for their ability to cause human disease. This proposal aims to study the mechanisms by which bacteria interact with fungi and by doing so, will identify important mechanisms of how microbes cause human illness and also uncover new targets for antibiotic development ....In hospitals and in nature, diverse microbes, such as bacteria and fungi, often live in close proximity to each other. Their interactions can either be helpful or detrimental to one another, and such interactions are likely important for their ability to cause human disease. This proposal aims to study the mechanisms by which bacteria interact with fungi and by doing so, will identify important mechanisms of how microbes cause human illness and also uncover new targets for antibiotic development.Read moreRead less
Diabolic Regulation Of Macrophage Cell Death Pathways By Legionella
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
The bacterial pathogen Legionella causes fatal pneumonia in immuno-compromised humans. Infections depend on a sophisticated secretion machinery that translocates hundreds of proteins into host cells. These proteins subvert several essential defense pathways, including cell death signals. This project will highlight how Legionella interfere with cell death pathways and control the survival of its host cells. These findings will facilitate the development of promising new anti-bacterial agents.