Elucidating the molecular basis of plant potyvirus resistance . Plant viruses are responsible for a large proportion of crop losses, and genetic resistance is currently the most effective means to control viral spread. This project investigates, on a molecular and structural level, host factors that plant viruses hijack during infection, and in particular, the mutations in these factors that confer resistance. We further aim to elucidate the mechanisms by which plant viruses overcome resistance ....Elucidating the molecular basis of plant potyvirus resistance . Plant viruses are responsible for a large proportion of crop losses, and genetic resistance is currently the most effective means to control viral spread. This project investigates, on a molecular and structural level, host factors that plant viruses hijack during infection, and in particular, the mutations in these factors that confer resistance. We further aim to elucidate the mechanisms by which plant viruses overcome resistance mediated by these host factors. A detailed understanding of the molecular interactions between plant viruses and their host will enable new, robust and more effective forms of resistance to be engineered. This work therefore has economic and environmental implications for agricultural productivity in Australia. Read moreRead less
Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from ....Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from sexually compatible species and short effective time spans in the field. Building on previous research, this project aims to characterise the molecular basis of the Toll/interleukin-1 receptor domain-mediated nicotinamide adenine dinucleotide (NAD+) cleavage and the structural architecture of plant NLR complexes. This knowledge will support the long-term objective of protecting crops from pathogens.Read moreRead less
Structural basis of plant immune receptor signaling. Plants detect invading pathogens and trigger immune responses in a process called “effector-triggered immunity”, in which pathogen effector (avirulence) proteins are recognized by plant resistance proteins, typically so-called “plant NLRs”. Ongoing work in the applicants’ laboratories has shown that oligomerization into “resistosomes” and NAD+ (nicotinamide adenine dinucleotide) cleavage play central roles in the process. Building on these dat ....Structural basis of plant immune receptor signaling. Plants detect invading pathogens and trigger immune responses in a process called “effector-triggered immunity”, in which pathogen effector (avirulence) proteins are recognized by plant resistance proteins, typically so-called “plant NLRs”. Ongoing work in the applicants’ laboratories has shown that oligomerization into “resistosomes” and NAD+ (nicotinamide adenine dinucleotide) cleavage play central roles in the process. Building on these data, the project aims to characterize the structures of the signaling molecules resulting from TIR (Toll/interleukin-1 receptor) domain-mediated NAD+ cleavage and the structural architecture of plant NLR resistosomes. This knowledge will support the long-term objective of protecting crops from pathogens.Read moreRead less
Role of Tau and Synapsin in clustering distinct synaptic vesicle pools. Neurotransmitter-containing synaptic vesicles (SVs) are highly enriched in specific locations of brain cells, called nerve terminals via an unknown mechanism. The clustering of SVs depend on the phosphorylation of an unknown set of proteins. Two key proteins have been identified for their phosphorylation pattern and their potential to form membraneless compartments: tau and synapsin. Using highly innovative single-molecule s ....Role of Tau and Synapsin in clustering distinct synaptic vesicle pools. Neurotransmitter-containing synaptic vesicles (SVs) are highly enriched in specific locations of brain cells, called nerve terminals via an unknown mechanism. The clustering of SVs depend on the phosphorylation of an unknown set of proteins. Two key proteins have been identified for their phosphorylation pattern and their potential to form membraneless compartments: tau and synapsin. Using highly innovative single-molecule super-resolution microscopy, this grant will uncover how tau and synapsin phosphorylation controls the clustering of SVs thereby regulating neurotransmitter release. This project uses improved nanoscopic technologies and international
collaborations to unveil novel avenues in our understanding of brain communication.Read moreRead less
Super-resolving neurotransmitter release machinery during priming. Understanding how neurons communicate in the brain is one of the most challenging feats in neuroscience. The assembly of the molecular machinery involved in communication is unknown. This grant aims to understand how priming molecules Munc18 and Munc13, undergo a series of molecular steps leading to the release of neurotransmitter. Using innovative single-molecule super-resolution imaging we will uncover how Munc18 and Munc13 are ....Super-resolving neurotransmitter release machinery during priming. Understanding how neurons communicate in the brain is one of the most challenging feats in neuroscience. The assembly of the molecular machinery involved in communication is unknown. This grant aims to understand how priming molecules Munc18 and Munc13, undergo a series of molecular steps leading to the release of neurotransmitter. Using innovative single-molecule super-resolution imaging we will uncover how Munc18 and Munc13 are spatially and temporally organised to mediate communication. By elucidating how nanoclustering of these essential proteins enables key steps, this grant will reveal how brain cells communicate. This may then provide new opportunities to optimise underlying functions such as cognition, sensory and motor processing.Read moreRead less
The mechanistic basis of tropism in an insecticidal pore-forming toxin . This project aims to answer a fundamental question regarding the mechanism of a recently discovered family of insecticidal protein complexes - how do these pore-forming proteins recognise and target specific hosts? The project will use an innovative, cross-disciplinary approach to determine the mechanisms of cellular recognition and uptake on a molecular scale. These outcomes have the potential to influence the use of ABC t ....The mechanistic basis of tropism in an insecticidal pore-forming toxin . This project aims to answer a fundamental question regarding the mechanism of a recently discovered family of insecticidal protein complexes - how do these pore-forming proteins recognise and target specific hosts? The project will use an innovative, cross-disciplinary approach to determine the mechanisms of cellular recognition and uptake on a molecular scale. These outcomes have the potential to influence the use of ABC toxins in many areas of biotechnology, delivering benefits including the development of new bioinsecticides for pest control and crop protection as well as in the development of bespoke protein delivery devices which may find use in biotechnological and therapeutic applications.Read moreRead less
Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodellin ....Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodelling is organised at a cell-type level is not understood. Here we aim to close this knowledge gap, using cutting-edge technology including bioconjugation and ultrasound-mediated cargo delivery. Together, this project aims to contribute to a deeper understanding of this major brain compartment in neuronal function. Read moreRead less
Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.Read moreRead less
Heat regulation by the fibre types in muscle. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the fibre types that make up skeletal muscles regulate heat generation against other muscle function, to maintain core body temperature and the normal movement and posture of the mammal. Project outcomes include defining, for the first time, how heat generation in the muscles o ....Heat regulation by the fibre types in muscle. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the fibre types that make up skeletal muscles regulate heat generation against other muscle function, to maintain core body temperature and the normal movement and posture of the mammal. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist with achieving a desired meat quality and yield in beef and other commercially important animals.Read moreRead less
Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project out ....Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist the production of meat by managing hypothermia and hyperthermia risk in agriculture.Read moreRead less