Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug ta ....Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug targets. This research will lead to new strategies in the design of improved anticancer drugs, which is an important Australian research priority that will promote and maintain good health, and provide potential commercial outcomes.Read moreRead less
How cells control autophagy during nutrient starvation and stress. This project aims to understand how human cells form autophagosomes during nutrient starvation and stress conditions, including bacterial invasion and mitochondrial dysfunction. Autophagy is a conserved intracellular degradation pathway which fungi, plants, insects and mammals use to respond to starvation and stress. Autophagy can provide nutrients by recycling cellular components, and protect cells from dysfunctional organelles ....How cells control autophagy during nutrient starvation and stress. This project aims to understand how human cells form autophagosomes during nutrient starvation and stress conditions, including bacterial invasion and mitochondrial dysfunction. Autophagy is a conserved intracellular degradation pathway which fungi, plants, insects and mammals use to respond to starvation and stress. Autophagy can provide nutrients by recycling cellular components, and protect cells from dysfunctional organelles and invading pathogens by mediating their removal. The autophagosome is a vesicular membrane structure important in autophagy by delivering material destined for degradation to the lysosome. Better understanding how plant and human cells protect themselves during starvation and stress is expected to benefit the environment and economy.Read moreRead less
Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replicati ....Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replication stress response where changes to the architecture of a cell nucleus, and movement of the genomic material inside, promotes repair of genomic damage that occurs during replication. The result of this project will be an understanding of fundamental biological processes that protect human genomes.Read moreRead less
Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the ....Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the degradation of proteins implicated in cell division and cell death. Expected outcomes include an increased understanding of how proteins are specifically selected for degradation. Protein degradation pathways operate with remarkable selectivity and this work is expected to illuminate the mechanisms of substrate targeting. The biochemical approaches will provide insight and impact in the areas of cell signaling, organelle biology and cell biology.Read moreRead less
Mitochondrial proteases and their contribution to protein homeostasis. This research will examine how a critically important cellular organelle known as the mitochondrion maintains its functional integrity by sensing and signalling protein perturbations. As mitochondrial dysfunction is central to a number of neurodegenerative diseases understanding the molecular biology of this fundamentally important cellular process could, in the future, provide for better health outcomes for an aging Australi ....Mitochondrial proteases and their contribution to protein homeostasis. This research will examine how a critically important cellular organelle known as the mitochondrion maintains its functional integrity by sensing and signalling protein perturbations. As mitochondrial dysfunction is central to a number of neurodegenerative diseases understanding the molecular biology of this fundamentally important cellular process could, in the future, provide for better health outcomes for an aging Australian population. The training of post-graduate students is an integral component of this study and thus will contribute to building national research capacity. International collaborations and new discoveries will also contribute to the recognition of Australian research.Read moreRead less
Identifying novel salinity tolerance mechanisms by spatial and temporal analysis of lipids in barley. Agrifood production faces the dual challenges of an increasing world population and the threats of abiotic stresses arising from climate change and the erosion of arable land. Cereals, the major food crops, are poorly adapted to tolerate most abiotic stresses, including salinity. This project applies new technologies investigating spatial and temporal biochemical mechanisms a model cereal, Horde ....Identifying novel salinity tolerance mechanisms by spatial and temporal analysis of lipids in barley. Agrifood production faces the dual challenges of an increasing world population and the threats of abiotic stresses arising from climate change and the erosion of arable land. Cereals, the major food crops, are poorly adapted to tolerate most abiotic stresses, including salinity. This project applies new technologies investigating spatial and temporal biochemical mechanisms a model cereal, Hordeum vulgare (barley), utilises to adapt and tolerate salinity. The aims are to investigate the role of specifically plasma membrane lipids modulating either signalling pathways or membrane fluidity that impacts on adaptation during salinity. The results will provide new leads for the development of cereal germplasm with increased salt tolerance.Read moreRead less
Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a ....Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a major class of host defence molecules, recognise microbial targets such as fungi, and exert a potent antimicrobial effect. Understanding the precise molecular mechanisms operating at both these host-pathogen interfaces this will provide novel avenues for the design of antiviral and antimicrobial agents.Read moreRead less
Crosstalk between cell survival and cell death pathways. This project aims to determine the precise molecular mechanisms underlying cell fate decisions. The dynamics between cell survival (autophagy) and cell death (apoptosis) are complex, involving significant crosstalk between these pathways. This is fundamentally important to cellular processes. Aberrant control of autophagy and apoptosis affects the function of all organisms as well as the development and treatment of diseases ranging from c ....Crosstalk between cell survival and cell death pathways. This project aims to determine the precise molecular mechanisms underlying cell fate decisions. The dynamics between cell survival (autophagy) and cell death (apoptosis) are complex, involving significant crosstalk between these pathways. This is fundamentally important to cellular processes. Aberrant control of autophagy and apoptosis affects the function of all organisms as well as the development and treatment of diseases ranging from cancer to heart disease. This project endeavours to advance our understanding of the proteins that interconnect autophagy and apoptosis. The results are expected to explain how cells determine their fate and inform future development of strategies to treat disease.Read moreRead less
The cell wall substrate delivery mechanisms in plants. This project aims to study the delivery of substrates plants need to biosynthesise sugar polymers. Sugar polymers play key structural and functional roles in plant development and determine quality for all plant-based products including food, textile fibres, building materials and renewable biomass. However, unknown mechanisms regulate and control the transport mechanisms that deliver the building blocks for polysaccharide biosynthesis. This ....The cell wall substrate delivery mechanisms in plants. This project aims to study the delivery of substrates plants need to biosynthesise sugar polymers. Sugar polymers play key structural and functional roles in plant development and determine quality for all plant-based products including food, textile fibres, building materials and renewable biomass. However, unknown mechanisms regulate and control the transport mechanisms that deliver the building blocks for polysaccharide biosynthesis. This project is expected to increase understanding of nucleotide sugar transport and develop and enhance the biological toolbox for applications involving modelling and engineering of plants, synthesis of industrial biopolymers and production of functional foods.Read moreRead less
Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally inf ....Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally infected or oncogenically transformed cells. Outcomes of this work may contribute to development of novel anti-cancer and anti-viral therapies, diagnostic reagents and vaccines.Read moreRead less