Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved ....Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved and how neurons maintain their individuality during development, remodelling and ageing is unknown. The project aims to address this gap using a genetic approach and the nematode Caenorhabditis elegans as an experimental system. The results may provide insights into how the nervous system develops and functions.Read moreRead less
Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following ner ....Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following nervous system injury and the importance of microtubule modifying proteins in promoting regeneration. This should provide significant benefits in our understanding of the cellular mechanisms behind nervous system repair, and offer new approaches for promoting regeneration after injury.Read moreRead less
The tau interactome. This project aims to decipher tau-dependent mechanisms at the molecular level to understand its pivotal role in neuronal integrity and function. Tau is a predominantly axonal protein with microtubule stabilising properties and has been implicated in several neurodegenerative disorders, including Alzheimer’s disease. Knowledge of its other physiological roles in the brain is limited, although it seems to be involved in signalling processes. The expected outcome of this study ....The tau interactome. This project aims to decipher tau-dependent mechanisms at the molecular level to understand its pivotal role in neuronal integrity and function. Tau is a predominantly axonal protein with microtubule stabilising properties and has been implicated in several neurodegenerative disorders, including Alzheimer’s disease. Knowledge of its other physiological roles in the brain is limited, although it seems to be involved in signalling processes. The expected outcome of this study is a deeper understanding of brain function during development and aging, which may ultimately contribute to new preventive treatments and medical care strategies.Read moreRead less
Discovering Novel Molecules That Regulate Axonal Degeneration.
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
The axon is the primary signaling component of every neuron and is essential for normal function. Axonal degeneration is a key early pathological hallmark of Alzheimer’s disease. We lack a basic understanding of molecules that regulate this process. Such knowledge is essential for the development of treatments and therapies for dementia and the preservation of healthy ageing. I aim to discover the molecules that regulate axonal degeneration and study their function.
A novel click chemistry approach to identify learning and memory molecules. This project seeks to contribute to a deeper understanding at a molecular level of how memory is stored in neurons. Long-term memories do not form immediately after learning. Initially fragile, they become resistant to disruption through a process known as memory consolidation. In a second process, termed reconsolidation, pre-established memories are updated and re-stored. Both processes depend on protein synthesis, but ....A novel click chemistry approach to identify learning and memory molecules. This project seeks to contribute to a deeper understanding at a molecular level of how memory is stored in neurons. Long-term memories do not form immediately after learning. Initially fragile, they become resistant to disruption through a process known as memory consolidation. In a second process, termed reconsolidation, pre-established memories are updated and re-stored. Both processes depend on protein synthesis, but little is known about the particular sets of proteins that are involved. The project plans to apply a novel biochemical protocol to a newly established transgenic mouse model that allows the visualisation and identification of newly synthesised proteins in the hippocampus, a brain area that is critical in memory formation.Read moreRead less
Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during developmen ....Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during development, test whether synaptic activation of receptors is required for these changes and define the pattern of activity-dependent changes in gene expression necessary for developmental changes in synaptic transmission. Understanding this interaction between synaptic phenome and activity-dependent genomic expression will expand our understanding of brain development and function.Read moreRead less
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.
Discovery Early Career Researcher Award - Grant ID: DE130101591
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Novel postsynaptic functions of the microtubule-associated protein tau. The protein tau is present in abnormal deposits in brains of individuals with dementia. The main aim of this project is to unravel and understand in detail new roles of tau in neurons and thus shed new light into normal brain function. Understanding these new functions of tau will aid in identifying new ways to treat these debilitating diseases.
Improving neuronal cell function with cell permeable copper complexes. Metal-based drugs offer an exciting new approach to treatment of neurodegeneration. However, little is known about how cells metabolise these drugs and this information is critical for further drug development. This project will determine how metal-based drugs are metabolised by neuronal cells and how this may result in therapeutic benefit.
Cellular mechanisms that protect against copper-bound beta-amyloid. This project will investigate some of the brain’s own mechanisms for protecting itself against Alzheimer’s disease. Understanding these mechanisms will be important for developing future therapeutic strategies for treating Alzheimer’s disease.