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
Molecular mechanisms determining the lipid composition of synapses. Synapses between neurons play a key role in all functions of the nervous system including learning and memory. They are mostly composed of the unique combination of proteins and lipids, which function together to enable neurotransmission. While the molecular mechanisms determining the protein composition of synapses are well characterised, the mechanisms defining the lipid composition of synapses remain unknown. The project will ....Molecular mechanisms determining the lipid composition of synapses. Synapses between neurons play a key role in all functions of the nervous system including learning and memory. They are mostly composed of the unique combination of proteins and lipids, which function together to enable neurotransmission. While the molecular mechanisms determining the protein composition of synapses are well characterised, the mechanisms defining the lipid composition of synapses remain unknown. The project will use advanced techniques of neuroscience and lipid research to determine the mechanisms of lipid transport and retention at synapses. The project is expected to generate new knowledge about the fundamental mechanisms of brain function, which will be useful for developing new therapeutics enhancing the brain power.Read moreRead less
A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project a ....A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project aims to use sensory neurons derived from human stem cells to develop and optimise assays that can be used to study the pharmacology and function of human sensory neurons in vitro. This enhances access to critical model systems and technology platforms and removes the need for isolation of cells from cadavers. Read moreRead less
Regulation of activity-induced glutamate receptor trafficking in neurons. Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate the role of a calcium binding protein i ....Regulation of activity-induced glutamate receptor trafficking in neurons. Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate the role of a calcium binding protein in controlling glutamate receptor trafficking in neurons. The outcomes will enhance our understanding of how neural plasticity is generated and maintained, knowledge that is critical for our understanding of cellular correlates of information, sensory and motor processing, as well as learning, memory and cognition. 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
Discovery Early Career Researcher Award - Grant ID: DE180100206
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Intelligently linking nanoscience to neuroscience with glycan biology. This project aims to provide a comprehensive description of the unique cell-surface glycan expression on inflamed neurons, astrocytes, microglia and oligodendrocytes. This project will use glycan profiling data to engineer luminescent nanoparticles with superior neuroimaging qualities for cell type-specific in vivo targeting and drug delivery in the central nervous system. The project outcomes are expected to improve our fund ....Intelligently linking nanoscience to neuroscience with glycan biology. This project aims to provide a comprehensive description of the unique cell-surface glycan expression on inflamed neurons, astrocytes, microglia and oligodendrocytes. This project will use glycan profiling data to engineer luminescent nanoparticles with superior neuroimaging qualities for cell type-specific in vivo targeting and drug delivery in the central nervous system. The project outcomes are expected to improve our fundamental understanding of neurobiological cell-surfaces.Read moreRead less
Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting ....Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting them in mice, testing for developmental, cognitive and motor effects, and characterising the structures with which they are associated. The results of the project are expected to open new vistas in neuroscience, contributing to understanding the molecular basis of brain function and the 'dark matter' of the genome.Read moreRead less
Understanding How the Hungry Brain Regulates Metabolism. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This process is orchestrated by neurons in the hypothalamus of the brain. This project aims to determine the role of the extracellular matrix that surrounds hypothalamic neurons and how this regulates energy homeostasis, an area of science that is completely unexplored. This project expects to identify the composition the extracellular m ....Understanding How the Hungry Brain Regulates Metabolism. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This process is orchestrated by neurons in the hypothalamus of the brain. This project aims to determine the role of the extracellular matrix that surrounds hypothalamic neurons and how this regulates energy homeostasis, an area of science that is completely unexplored. This project expects to identify the composition the extracellular matrix within the hypothalamus and discover how it regulates energy homeostasis. The outcomes of this project are to provide new knowledge in understanding how the brain regulates metabolism, to promote population health & wellbeing, develop new technologies and training the next generation of researchers.Read moreRead less
Turning back the clock on brain cell aging. This proposal aims to determine the role of fundamental epigenetic mechanisms in the process of aging and whether modulation of the epi-genome underpins an improvement in cognitive function. It combines the fields of epigenetics, neurosciences and mathematics to delineate the dynamics of DNA methylation and histone modification marking on the transcriptome during normal, healthy aging. The outcomes will provide significant new knowledge of the variable ....Turning back the clock on brain cell aging. This proposal aims to determine the role of fundamental epigenetic mechanisms in the process of aging and whether modulation of the epi-genome underpins an improvement in cognitive function. It combines the fields of epigenetics, neurosciences and mathematics to delineate the dynamics of DNA methylation and histone modification marking on the transcriptome during normal, healthy aging. The outcomes will provide significant new knowledge of the variable cognitive decline that occurs in healthy aging and why some populations age less successfully than others do. Better understanding of the impact of environmental change on the biology of aging has potential community benefits.Read moreRead less