Discovery Early Career Researcher Award - Grant ID: DE190100565
Funder
Australian Research Council
Funding Amount
$422,107.00
Summary
A novel role for saturated fatty acids in learning and memory. This project aims to characterise the novel role of the phospholipase A1 pathway in neurotransmission, generating new knowledge on how the saturated fatty acid changes in neurons affect the mobility of neurotransmitter receptors and synaptic vesicles. Learning and memory are thought to result from long-lasting changes in synaptic strength. Whereas the role of polyunsaturated fatty acids in these functions is well known, recent findin ....A novel role for saturated fatty acids in learning and memory. This project aims to characterise the novel role of the phospholipase A1 pathway in neurotransmission, generating new knowledge on how the saturated fatty acid changes in neurons affect the mobility of neurotransmitter receptors and synaptic vesicles. Learning and memory are thought to result from long-lasting changes in synaptic strength. Whereas the role of polyunsaturated fatty acids in these functions is well known, recent findings suggest an unprecedented role for the generation of saturated free fatty acids by phospholipase A1-enzyme. Expected outcomes of this project will be to provide novel conceptual insights into learning, memory and brain capacity.Read moreRead less
Operation of nerve cell networks in the neocortex. In humans, intellectual disabilities occur when nerve cells in the neocortex, the most complicated area of the brain, fail to function correctly. The goal of this project is to understand how neocortical areas communicate and how changes in the structure of neurons disturb their function; work that will lead to a better understanding of the operation of the neocortex.
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
Intra and intermolecular steps underpinning vesicular priming. This project aims to discover how secretory vesicles fuse with the plasma membrane, a process called priming. The fusion of secretory vesicles by exocytosis underpins neuronal communication. Despite efforts to understand vesicular fusion, how these vesicles become fusion-competent upon arrival at the plasma membrane is unknown. This project will use single molecule imaging to assess mobility changes of key priming molecules and uncov ....Intra and intermolecular steps underpinning vesicular priming. This project aims to discover how secretory vesicles fuse with the plasma membrane, a process called priming. The fusion of secretory vesicles by exocytosis underpins neuronal communication. Despite efforts to understand vesicular fusion, how these vesicles become fusion-competent upon arrival at the plasma membrane is unknown. This project will use single molecule imaging to assess mobility changes of key priming molecules and uncover their diffusional signature during priming. It intends to build a comprehensive model of molecular interactions that make a recently docked vesicle fusion-competent. This understanding is key to unravelling how the brain worksRead moreRead less
Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly qui ....Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly quiescent, dividing rarely to ensure that they are not prematurely exhausted. However, the factors that maintain this quiescence are very poorly defined. The project aims to understand how stem cell quiescence is controlled at both a molecular and cellular level in vivo within the adult mouse brain.Read moreRead less
Transcriptional regulation of brain size during development. This project aims to understand the fundamental mechanisms through which intermediate progenitor cell (IPC) formation is regulated within the cerebral cortex. The cerebral cortex plays a key role in functions central to our existence, including emotion, behaviour, learning and memory. During development, cortical neural stem cells produce neurons via IPCs. This project expects to discover the genetic programs regulating neuronal produc ....Transcriptional regulation of brain size during development. This project aims to understand the fundamental mechanisms through which intermediate progenitor cell (IPC) formation is regulated within the cerebral cortex. The cerebral cortex plays a key role in functions central to our existence, including emotion, behaviour, learning and memory. During development, cortical neural stem cells produce neurons via IPCs. This project expects to discover the genetic programs regulating neuronal production, providing significant conceptual advances in this key field. This will provide significant benefits, such as enhancing our understanding of how overall brain size is regulated during development.Read moreRead less
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
Molecules and mechanisms regulating axonal degeneration and regeneration in Caenorhabditis elegans neurons. Understanding the molecular mechanisms underlying nerve degeneration and regeneration is essential to tackle and provide treatment for neurodegenerative diseases and injury of the nervous system. This project aims to discover, using a genetic approach and a simple animal model system, the molecules regulating these crucial biological processes.
Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the ....Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the true nature of brain adaptation.Read moreRead less
The long-term consequences of toluene exposure on the maturing brain. Inhalant abuse is a significant problem especially among adolescent and indigenous communities. This project will provide insights into the long-term neurobiological consequences following inhalant exposure during adolescence when critical aspects of brain development are still occurring and how these may relate to altered behaviour in adulthood.