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
Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innov ....Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innovative genome editing, mathematical modelling and proteomic approaches, to study how biochemical modifications of a key protein called tau help encode and retrieve memories. These molecular insights will make a significant advance in the current understanding of a brain function that is essential to all human activities.Read moreRead less
Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, wh ....Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, which is an essential component of human and animal life. This research provides significant benefits in understanding the biology behind memory and in maintaining memory capacity in ageing.
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Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport syst ....Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport systems located in the bacterial plasma membrane, beneath the cell wall, facilitating Zn uptake by the bacterium. The aim of this project is to conduct comprehensive molecular characterization of the interactions between Pht proteins, Zn and ABC transporters, and the role of the histidine triad motifs in these interactions.Read moreRead less
Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without ....Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without accumulating a toxic excess (metal homeostasis) is poorly understood. Discovering the roles of metal ions in bacterial cells will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
TREX-mediated nuclear mRNA export in neuronal differentiation and function. This project aims to study nucleus-to-cytoplasm information flow and the cellular toolbox required for this process. To ensure competitive growth and survival, plant and animal cells have sophisticated mechanisms of information transfer. One such process is efficient export of molecules from the cell nucleus (the coding space) to the cell cytoplasm (the protein synthesis space). This project will use a cell-based system ....TREX-mediated nuclear mRNA export in neuronal differentiation and function. This project aims to study nucleus-to-cytoplasm information flow and the cellular toolbox required for this process. To ensure competitive growth and survival, plant and animal cells have sophisticated mechanisms of information transfer. One such process is efficient export of molecules from the cell nucleus (the coding space) to the cell cytoplasm (the protein synthesis space). This project will use a cell-based system that can precisely control different aspects of the toolbox performance to understand this process. The knowledge and resources generated can be used to develop products or services with tangible economic and health benefits.Read moreRead less
Nanoparticle regulation of DNA replication and repair pathways. This project aims to understand how physical and chemical properties of nanoparticles influence how cells respond with respect to maintenance of their DNA integrity. It will use an innovative set of cross-disciplinary methodologies to link what nanoparticle parameters can lead to a benign fate in the environment. The project expects to generate new knowledge of how our ecosystem can be fundamentally impacted by nanoscale materials. ....Nanoparticle regulation of DNA replication and repair pathways. This project aims to understand how physical and chemical properties of nanoparticles influence how cells respond with respect to maintenance of their DNA integrity. It will use an innovative set of cross-disciplinary methodologies to link what nanoparticle parameters can lead to a benign fate in the environment. The project expects to generate new knowledge of how our ecosystem can be fundamentally impacted by nanoscale materials. The intended outcome of the project is to position Australia as a world leader in the manufacture of environmentally benign, advanced nano-scale materials. This is expected to provide economic benefits for Australian manufacturing while ensuring preservation of environmental health.Read moreRead less
Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less