The biogenesis of bacterial outer membranes; how bacteria build their surface membranes. The outer membrane protects probiotic bacteria in the human intestine and enables pathogenic bacteria to cause infectious diseases. We will determine bacteria build their outer membranes - outstanding training opportunities come through cutting edge technology and the development of skills not common in Australia.
Structural analysis of a novel plasma membrane coat complex. The plasma membrane of mammalian cells forms a crucial barrier between the cell and the outside world. This project investigates how a newly-discovered family of proteins work together to generate specialised regions of the plasma membrane called caveolae.
Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specif ....Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specific enzymes. The expected outcome will be to re-define the archetypical autophagy pathway and characterise novel mechanisms by which it is controlled. This project will reveal new fundamental biological processes, and act as a framework for developing new imaging modalities and tools for studying autophagy.Read moreRead less
New targets for antiviral therapies. The ability of dangerous viruses to cause lethal disease depends on their capacity to evade the immune system of infected hosts. This project will uncover at the molecular level the strategies used by viruses to disable immune responses; this will identify new ways to treat incurable diseases, by disabling the virus' defences against the immune system.
The role of actin in driving bulk endocytosis in neurons and neurosecretory cells. Synaptic release of neurotransmitter is essential for neuronal communication. Following fusion, synaptic vesicle membrane is incorporated into the plasma membrane and retrieved by endocytosis to recover both lipids and essential vesicular proteins. The project will characterise how the actin cytoskeleton perform this function.
Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds ....Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds of fusion. This recycling process ensures that neurons communicate efficiently, however the underpinning mechanism is unknown. This project aims to use a recently developed single synaptic vesicle super-resolution tracking method to establish how Myosin-VI and Synapsin-IIa orchestrate this recycling in central and peripheral neurons. It will explain how neurons manage to preserve their ability to communicate.Read moreRead less
Protein trafficking pathways in fungal rust pathogens of plants. This project aims to investigate protein trafficking pathways in fungal rusts of plants. These are devastating diseases that cause major losses in agricultural crops including wheat. Little is known of how these fungi form long and intimate relationships with plants to extract their nutrients. Using both model and agriculturally important fungi, the project will try to identify proteins that are transferred within the fungus and to ....Protein trafficking pathways in fungal rust pathogens of plants. This project aims to investigate protein trafficking pathways in fungal rusts of plants. These are devastating diseases that cause major losses in agricultural crops including wheat. Little is known of how these fungi form long and intimate relationships with plants to extract their nutrients. Using both model and agriculturally important fungi, the project will try to identify proteins that are transferred within the fungus and to the plant host to modify the infection. It will also identify fungal proteins needed to deliver trafficked proteins to plants. These discoveries ultimately may be translated into control strategies for these costly diseases.Read moreRead less
Deciphering the cellular defences against aggregating proteins in human disease. Cells have inbuilt defences for coping with proteins that bend into abnormal sticky shapes that form toxic clusters. In many diseases, including Huntington's, the clusters severely damage nerve cells. This project will identify the genes and mechanisms cells use to protect themselves from toxic clusters, which could provide new therapeutic targets.
Defining systems that clear dangerous misfolded proteins from body fluids. The project intends to establish how the human body defends itself against protein-folding related disease and loss of quality of life. Exposure to everyday physical and chemical stresses can cause proteins to lose their normal shape and become misfolded. Misfolded proteins are causally involved in human ageing and serious diseases (for example, Alzheimer's disease). However, the body does have a protective system that cl ....Defining systems that clear dangerous misfolded proteins from body fluids. The project intends to establish how the human body defends itself against protein-folding related disease and loss of quality of life. Exposure to everyday physical and chemical stresses can cause proteins to lose their normal shape and become misfolded. Misfolded proteins are causally involved in human ageing and serious diseases (for example, Alzheimer's disease). However, the body does have a protective system that clears dangerous misfolded proteins from body fluids. Using cutting-edge approaches and a novel animal model, the project aims to establish how this system works. The outcomes are expected to improve understanding of the molecular processes affecting human ageing and disease and strengthen the framework needed to develop better strategies to combat these.Read moreRead less
Characterisation of membrane protein ubiquitination by MARCH ligases. The goal of the project is to understand how a family of enzymes called MARCHs regulate expression and localisation of immunoregulatory receptors within cells by post-translational addition of a small protein tag called Ubiquitin. The aims are to decipher the ubiquitination patterns produced by the MARCHs; identify the E2 ligases used by the MARCHs to produce distinct Ub codes; and apply a new proteomic pipeline to identify no ....Characterisation of membrane protein ubiquitination by MARCH ligases. The goal of the project is to understand how a family of enzymes called MARCHs regulate expression and localisation of immunoregulatory receptors within cells by post-translational addition of a small protein tag called Ubiquitin. The aims are to decipher the ubiquitination patterns produced by the MARCHs; identify the E2 ligases used by the MARCHs to produce distinct Ub codes; and apply a new proteomic pipeline to identify novel representative MARCH substrates in mice deficient in six different MARCHs. It is anticipated the project will reveal novel insights into a fundamental cell biological process of major significance for regulation of protein expression and trafficking in cells of the immune system.Read moreRead less