Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned ....Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned about the development of these parasites. The expected outcomes are an understanding of the mechanisms of sexual differentiation and a functional characterisation of novel sex-specific molecules. This will provide significant benefits, such as pivotal prerequisites for new approaches to parasite intervention.Read moreRead less
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
How do apicomplexan parasites steal amino acids from their hosts? The single-celled parasites that cause malaria and toxoplasmosis are adept at stealing nutrients from the host animals that they infect. How they do this is, however, poorly understood. This project seeks to identify the processes by which these parasites scavenge amino acids, an essential class of nutrient, from their hosts. Using innovative experimental approaches, the project aims to identify and characterise the parasite prote ....How do apicomplexan parasites steal amino acids from their hosts? The single-celled parasites that cause malaria and toxoplasmosis are adept at stealing nutrients from the host animals that they infect. How they do this is, however, poorly understood. This project seeks to identify the processes by which these parasites scavenge amino acids, an essential class of nutrient, from their hosts. Using innovative experimental approaches, the project aims to identify and characterise the parasite proteins that mediate the uptake of different amino acids into the parasite. The intended outcomes of the project are to provide comprehensive insights into a fundamental aspect of parasite biology, and inform strategies to treat the diseases caused by these parasites by cutting off their nutrient supply.Read moreRead less
Probing antimicrobial drug resistance by multimodal molecular analysis. This project aims to investigate drug resistance in microbial agents. With the emergence of "super bugs" there is a need to understand the biochemistry of antimicrobial resistance. Combining vibrational spectroscopic approaches and metabolomic techniques, the project will investigate cell populations, single cells and subcellular structures in search of biomarkers for drug resistance. The discovery of such biomarkers could l ....Probing antimicrobial drug resistance by multimodal molecular analysis. This project aims to investigate drug resistance in microbial agents. With the emergence of "super bugs" there is a need to understand the biochemistry of antimicrobial resistance. Combining vibrational spectroscopic approaches and metabolomic techniques, the project will investigate cell populations, single cells and subcellular structures in search of biomarkers for drug resistance. The discovery of such biomarkers could lead to improved disease management and eradication programs through identification and treatment of drug resistant pathogens in individuals that have the potential to re-infect the community.Read moreRead less
Chemo-sensation in Ascaris infection. This project aims to show the role of chemo-sensation as an equally important target for worm control, and explore pathways to prevent infection. Parasitic worms cost global food/textile industry more than $100 billion dollars per year, and cause disease in more than 1 billion people and domesticated animals world-wide. This project will use a combination of imaging, systems biology, chemical biology and microfluidic methods to provide significant benefits, ....Chemo-sensation in Ascaris infection. This project aims to show the role of chemo-sensation as an equally important target for worm control, and explore pathways to prevent infection. Parasitic worms cost global food/textile industry more than $100 billion dollars per year, and cause disease in more than 1 billion people and domesticated animals world-wide. This project will use a combination of imaging, systems biology, chemical biology and microfluidic methods to provide significant benefits, such as exploring Ascaris chemo-sensation during larval migration, identify the key host queues and parasite genes regulating this process, and probe helminth chemosensation as a novel target for anti-parasitic treatments.Read moreRead less
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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Chemical probes to dissect the cell cycle of globally important parasites . This project aims to develop new reagents, called chemical probes, to visualise key biological events in globally important pathogens. We will use innovative chemistry to modify the building blocks of DNA and provide researchers with essential tools to 'see' DNA synthesis in order to study growth and replication of pathogens in combination with microscopy. This project expects to support a major technical advance that wi ....Chemical probes to dissect the cell cycle of globally important parasites . This project aims to develop new reagents, called chemical probes, to visualise key biological events in globally important pathogens. We will use innovative chemistry to modify the building blocks of DNA and provide researchers with essential tools to 'see' DNA synthesis in order to study growth and replication of pathogens in combination with microscopy. This project expects to support a major technical advance that will address important gaps in our understanding of many pathogens (e.g. those that cause malaria and tuberculosis), at both the cellular and molecular levels. This should provide significant benefits by enabling researchers worldwide to identify new intervention opportunities that target unique aspects of pathogen biology.Read moreRead less
Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and ....Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and death are controlled. It combines methods we developed to track MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling MAIT cell survival/death and increase our fundamental understanding of cell death mechanisms of activated T cells.Read moreRead less
Koala retrovirus epidemic: genetic diversity, genome invasion and disease. This project aims to study the role the koala retrovirus (KoRV) plays in disease of koalas and the mechanisms of transmission in the advancing epidemic. This project aims to firstly, identify mechanisms that govern the rate of southerly dissemination for the ongoing KoRV epidemic and secondly, identify virulence factors that endow KoRV subtypes with distinct modes of transmission that contribute to disease outcome. Unders ....Koala retrovirus epidemic: genetic diversity, genome invasion and disease. This project aims to study the role the koala retrovirus (KoRV) plays in disease of koalas and the mechanisms of transmission in the advancing epidemic. This project aims to firstly, identify mechanisms that govern the rate of southerly dissemination for the ongoing KoRV epidemic and secondly, identify virulence factors that endow KoRV subtypes with distinct modes of transmission that contribute to disease outcome. Understanding the mechanisms behind this advancing epidemic will have important implications for conservation efforts.Read moreRead less
Structural Characterisation of the Type IX Secretion System. The Type IX Secretion System present in diverse bacteria of veterinary, agricultural, environmental and industrial importance enables effector proteins to be secreted and attached to the cell surface where they contribute to disease pathogenesis or degrade biopolymers of commercial interest. This project aims to determine the structure and assembly mechanism of this complex secretion nanomachine comprising 15 different proteins using s ....Structural Characterisation of the Type IX Secretion System. The Type IX Secretion System present in diverse bacteria of veterinary, agricultural, environmental and industrial importance enables effector proteins to be secreted and attached to the cell surface where they contribute to disease pathogenesis or degrade biopolymers of commercial interest. This project aims to determine the structure and assembly mechanism of this complex secretion nanomachine comprising 15 different proteins using state of the art microscopy. Knowledge of the structure will greatly enhance our understanding of secretion mechanisms and our ability to both inhibit the system to treat disease in animals or manipulate the system for industrial applications providing future economic and environmental benefits to our nation.Read moreRead less