Cell Therapy For The Prevention And Treatment Of Invasive Filamentous Fungal Infections In Patients With Haematological Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$987,873.00
Summary
Common fungi in the environment do not cause disease in healthy individuals. They are however responsible for fatal infections leading to death when the immune system is impaired following treatment for blood cancers. This project aims to restore defects in the immune system of these patients by giving them cells that have been grown to recognize and kill fungus.
Understanding the T cell repertoire in health and disease. Immune recognition of viruses usually involves a large number of different 'killer T cells' that kill cells infected by virus. However, during prolonged infection or in the elderly the number of different killer T cells that recognise the virus is greatly reduced. This reduction in the diversity of the immune response allows the virus to avoid immune recognition, and leads to more severe infection. We aim to understand how diversity is ....Understanding the T cell repertoire in health and disease. Immune recognition of viruses usually involves a large number of different 'killer T cells' that kill cells infected by virus. However, during prolonged infection or in the elderly the number of different killer T cells that recognise the virus is greatly reduced. This reduction in the diversity of the immune response allows the virus to avoid immune recognition, and leads to more severe infection. We aim to understand how diversity is generated in the immune response, and how it becomes narrowed with age or prolonged infection. This information can be used to design vaccines for persistent infections such as HIV, and to improve immune control of infection in the elderly.Read moreRead less
A novel approach to fighting fungal infections: targeted disruption of hydrophobin monolayers. Fungal infestations of important crops such as cotton cause large economic losses to Australian agriculture while in the medical sector, fungal infections are responsible for high levels of mortality in immunocompromised patients. Our research will provide a new approach to fighting fungal infections by targeting the hydrophobin proteins, which form a robust coating on fungal aerial structures, such as ....A novel approach to fighting fungal infections: targeted disruption of hydrophobin monolayers. Fungal infestations of important crops such as cotton cause large economic losses to Australian agriculture while in the medical sector, fungal infections are responsible for high levels of mortality in immunocompromised patients. Our research will provide a new approach to fighting fungal infections by targeting the hydrophobin proteins, which form a robust coating on fungal aerial structures, such as spores. This layer is critical for fungal growth and reproduction and confers water resistance and tolerance to harsh conditions. Our work seeks to develop reagents that can specifically block regions on the protein that are responsible for forming this coating.
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Unravelling cell wall polysaccharide biosynthesis in pathogenic zygomycetes. This project aims to define mechanisms that control cell wall composition and stability in Rhizopus oryzae, a zygomycete fungus responsible for life-threatening human infections. The biochemical properties and function of vital enzymes involved in a newly discovered cell wall polysaccharide biosynthetic pathway will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology an ....Unravelling cell wall polysaccharide biosynthesis in pathogenic zygomycetes. This project aims to define mechanisms that control cell wall composition and stability in Rhizopus oryzae, a zygomycete fungus responsible for life-threatening human infections. The biochemical properties and function of vital enzymes involved in a newly discovered cell wall polysaccharide biosynthetic pathway will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology and structural biology. Expected outcomes include new knowledge on the enzymes that synthesise major fucose-based carbohydrates, to guide the future development of novel strategies for antifungal therapies. The data will also be applicable to animal protection from related zygomycete pathogens.
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Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensi ....Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensins a number of proteinase inhibitors were identified that act synergistically with NaD1. This project aims to identify the molecular basis of this synergy which is expected to lead to better control of fungal diseases of crops and in humans.Read moreRead less
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.