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
Exploiting microbial metabolites to understand fungal biology. The project aims to investigate the principles of hyphal growth in fungi, by studying the mechanisms of action of a bacteria-derived compound that inhibits hyphae. Changing cell shape between yeast and hyphae is a prototype developmental switch enabling fungi to escape stressful environments, while hyphal invasion promotes fungal infections of animals and plants that endanger food security and biodiversity. By using interdisciplinary ....Exploiting microbial metabolites to understand fungal biology. The project aims to investigate the principles of hyphal growth in fungi, by studying the mechanisms of action of a bacteria-derived compound that inhibits hyphae. Changing cell shape between yeast and hyphae is a prototype developmental switch enabling fungi to escape stressful environments, while hyphal invasion promotes fungal infections of animals and plants that endanger food security and biodiversity. By using interdisciplinary approaches of microbiology and chemistry, the expected outcomes are to generate deep knowledge of an important microbial process and how it could be modulated, characterise a new bacterial compound and build research capacity at the nexus of biology and chemistry to benefit discoveries in academia and industry.Read moreRead less
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
Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is ....Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is easily studied in the laboratory by advanced genetic techniques to identify the ways in which genes are turned on and off in response to changes in the nutrients available. By comparing DNA sequences the results are readily applied to fungi of economic importance.Read moreRead less
Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immu ....Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immune cells and bacteria. By utilising a powerful combination of molecular and systems biology with molecular genetics and imaging, the project outcomes should foster interdisciplinary collaborations and build capacity for fundamental and applied research to benefit academia and industry, locally and globally.Read moreRead less
Cell wall structure and dynamics in emerging fungal pathogens of crops. The project aims to understand the role of fungal cell wall biosynthetic enzymes in cell wall stability. The fungal cell wall is a dynamic structure whose composition constantly changes in response to biotic and abiotic stresses and at different developmental stages. The devastating fungal crop pathogen Fusarium graminearum is responsible for the head blight disease in cereals. The project aims to understand the molecular ev ....Cell wall structure and dynamics in emerging fungal pathogens of crops. The project aims to understand the role of fungal cell wall biosynthetic enzymes in cell wall stability. The fungal cell wall is a dynamic structure whose composition constantly changes in response to biotic and abiotic stresses and at different developmental stages. The devastating fungal crop pathogen Fusarium graminearum is responsible for the head blight disease in cereals. The project aims to understand the molecular events that govern metabolism and dynamics of the cell wall of F. graminearum. The project also plans to characterise the molecular interactions involved in plant defence against fungal pathogens and fungal responses to plant immune factors called defensins. Expected long-term outcomes include the development of novel strategies for disease control and crop protection.Read moreRead less
BIOSYNTHESIS OF A FUNGAL TOXIN AND ITS ROLE IN PLANT DISEASE. This project will determine how an important class of toxic molecules, epipolythiodioxopiperazines (EPTs), are made by fungi. Knowledge of the domains and actions of these genes in the biosynthetic pathway may lead to the ability to engineer secondary metabolites with altered specificity, and drugs that alleviate symptoms of secondary fungal toxicoses associated with leukemia, organ transplants and HIV AIDS. Also this project will a ....BIOSYNTHESIS OF A FUNGAL TOXIN AND ITS ROLE IN PLANT DISEASE. This project will determine how an important class of toxic molecules, epipolythiodioxopiperazines (EPTs), are made by fungi. Knowledge of the domains and actions of these genes in the biosynthetic pathway may lead to the ability to engineer secondary metabolites with altered specificity, and drugs that alleviate symptoms of secondary fungal toxicoses associated with leukemia, organ transplants and HIV AIDS. Also this project will also elucidate the role of an EPT, sirodesmin, in blackleg of canola, a disease that costs the Australian canola industry up to $50 million in losses annually. Outcomes of this project may lead to novel blackleg disease control strategies. Read moreRead less
3'UTR switching in eukaryotic cells. The project aims to uncover conserved features fundamental to the mechanism and function of post-transcriptional gene-expression control. RNA systems interface the executive functions of DNA and the worker functions of proteins. mRNA often dictates the level, timing and location of protein synthesis. This project will use RNA-sequencing and bespoke bioinformatics to probe global RNA-dynamics. Mixing yeast-genetics with RNA-technologies, it focuses on 3’ untra ....3'UTR switching in eukaryotic cells. The project aims to uncover conserved features fundamental to the mechanism and function of post-transcriptional gene-expression control. RNA systems interface the executive functions of DNA and the worker functions of proteins. mRNA often dictates the level, timing and location of protein synthesis. This project will use RNA-sequencing and bespoke bioinformatics to probe global RNA-dynamics. Mixing yeast-genetics with RNA-technologies, it focuses on 3’ untranslated region (UTR) dynamics in eukaryotic cell biology. This project expects to significantly advance the understanding of eukaryotic gene function and gene regulation, critical in an age of personalised genomic medicine.Read moreRead less
My enemy’s enemy is my friend: The genetics of major plant pathogen killers. Fungi are devastating agents of crop diseases. These plant pathogens, in turn, are often parasitized by other fungi in the field. The project will focus on such interactions between powdery mildews, important pathogens of many crops and wild plants, and their common fungal parasites (Ampelomyces spp.) that have already been utilised as
biocontrol agents in crop protection. Genetic and genomic tools will be used to deter ....My enemy’s enemy is my friend: The genetics of major plant pathogen killers. Fungi are devastating agents of crop diseases. These plant pathogens, in turn, are often parasitized by other fungi in the field. The project will focus on such interactions between powdery mildews, important pathogens of many crops and wild plants, and their common fungal parasites (Ampelomyces spp.) that have already been utilised as
biocontrol agents in crop protection. Genetic and genomic tools will be used to determine if these parasites evolved by switching host from plants to plant pathogens. The project has the potential to make a ground-breaking discovery in this field, and also establish the starting point for new innovative methods to protect a wide diversity
of crops using these fungi or specific compounds derived from them.Read moreRead less
The effects of damage and repair of fungal DNA on animal and plant diseases. DNA damage and its repair are implicated in enhancing the ability of fungi to cause disease. These processes enable genomic changes that generate fungal strains better adapted to host colonisation. This project will identify factors that influence mutation, virulence and host adaptation in two model fungi that cause devastating diseases - a human pathogen, Cryptococcus neoformans, and a plant pathogen, Leptosphaeria mac ....The effects of damage and repair of fungal DNA on animal and plant diseases. DNA damage and its repair are implicated in enhancing the ability of fungi to cause disease. These processes enable genomic changes that generate fungal strains better adapted to host colonisation. This project will identify factors that influence mutation, virulence and host adaptation in two model fungi that cause devastating diseases - a human pathogen, Cryptococcus neoformans, and a plant pathogen, Leptosphaeria maculans. Since increases in global temperatures are expected to lead to emerging fungal diseases, understanding effects of damage and repair of fungal DNA on animal and plant diseases is key to designing disease control approaches.Read moreRead less