Unravelling the mechanism of vesicular docking in neurosecretory cells. The fusion of secretory vesicles (SVs) by exocytosis underpins neuronal and hormonal communication. The aim of this project is to unravel all the steps bringing these vesicles to the plasma membrane where they dock. Specifically, we aim to unravel the role for the cytoskeleton in creating an interface where SV confinement leads to the appropriate pairing of molecules mediating the fusion between the vesicles and the plasma m ....Unravelling the mechanism of vesicular docking in neurosecretory cells. The fusion of secretory vesicles (SVs) by exocytosis underpins neuronal and hormonal communication. The aim of this project is to unravel all the steps bringing these vesicles to the plasma membrane where they dock. Specifically, we aim to unravel the role for the cytoskeleton in creating an interface where SV confinement leads to the appropriate pairing of molecules mediating the fusion between the vesicles and the plasma membrane. Unravelling these novel molecular mechanisms is essential for our understanding of neuronal function in the healthy nervous and hormonal systems.Read moreRead less
Biomagnification of the biotoxin BMAA in the environment. Using unique models and technics, the project aims to demonstrate that long-term exposure to the blue green algae toxin β-N-methylamino-l-alanine (BMAA) leads to uptake, accumulation and toxicity within the central nervous system. The risks for heath, mechanisms of contamination and toxicity of BMAA are very poorly understood. Algal blooms cost the Australian community more than $250 million each year and represent a major health issue fo ....Biomagnification of the biotoxin BMAA in the environment. Using unique models and technics, the project aims to demonstrate that long-term exposure to the blue green algae toxin β-N-methylamino-l-alanine (BMAA) leads to uptake, accumulation and toxicity within the central nervous system. The risks for heath, mechanisms of contamination and toxicity of BMAA are very poorly understood. Algal blooms cost the Australian community more than $250 million each year and represent a major health issue for human and fauna. This project aims to be the first to fully characterise BMAA mechanisms of contamination and neurotoxicity and to highlight the major environmental risk of exposure of human to BMAA. It also aims to develop new and unique detection and quantification tools for BMAA.Read moreRead less
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.
The role of tropomyosin in coordinated neurite branching. This project will explore how nerve cells generate a highly branched network of cell processes which allows all higher functions of the nervous system. We previously discovered the central role of a component of the cell architecture in determining the branching pattern and in this project expect to reveal the molecular basis for its function.
Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and ....Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and in vivo, we will be able to define the molecular changes in neurites that control neurite branching. This should provide significant benefits, such as gaining crucial insights into the mechanisms of forming complex neuronal networks.Read moreRead less
The mode of action of the haem protein neuroglobin in protecting nerve cells. Outcomes from this project will assist in developing new treatments for stroke and chronic degenerative brain disorders by characterising how the haem protein neuroglobin protects neurons of the central and peripheral nervous system from oxidative damage. This project will also develop pharmacological strategies to boost the concentration of neuroglobin in neurons.
Regulation of mRNA translation by the microtubule-associated protein Tau. This project aims to understand the molecular processes in a cell type and subcellular compartment that underlies learning and memory formation. Fundamental neuronal functions such as synaptic strengthening and memory formation are dependent on the tightly regulated process of protein translation. The kinase Fyn (which is localised to dendritic spines where memories are formed) activates the ERK/S6 pathway leading to massi ....Regulation of mRNA translation by the microtubule-associated protein Tau. This project aims to understand the molecular processes in a cell type and subcellular compartment that underlies learning and memory formation. Fundamental neuronal functions such as synaptic strengthening and memory formation are dependent on the tightly regulated process of protein translation. The kinase Fyn (which is localised to dendritic spines where memories are formed) activates the ERK/S6 pathway leading to massive translation of the scaffolding protein Tau. More importantly, the activation of this cascade is Tau-dependent. This project aims to determine how Tau activates this pathway, and to decipher the physiological role of the Tau/Fyn/Tau feedback loop. This will inform our understanding of the molecular regulation of learning and memory.Read moreRead less
Regulation of glutamate receptor dynamics in mammalian central neurons. This proposal aims to understand the molecular mechanisms of neuronal communication and how neurons modify their synaptic strength. Although these processes are essential for normal brain function, the precise underlying mechanisms are still not well understood. This project will combine biochemical, molecular and cell biological assays, as well as electrophysiological measurements, to provide mechanistic insights into the m ....Regulation of glutamate receptor dynamics in mammalian central neurons. This proposal aims to understand the molecular mechanisms of neuronal communication and how neurons modify their synaptic strength. Although these processes are essential for normal brain function, the precise underlying mechanisms are still not well understood. This project will combine biochemical, molecular and cell biological assays, as well as electrophysiological measurements, to provide mechanistic insights into the molecular processes that control glutamate receptor trafficking in the postsynaptic compartment. This will elucidate how neural plasticity is generated and maintained, information that is critical for our understanding of sensory processing, learning and memory throughout life.Read moreRead less
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes ....The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes to characterise the structure and function of a newly identified copper-dependent form of cell enzyme which could be involved in amplifying ubiquitin-tagged protein breakdown. Copper is essential for life in all domains. Identifying copper as a major regulator in protein clearance is important in understanding this fundamental biological machinery.Read moreRead less