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.
Axonal Fusion To Promote Nerve Repair: Molecules And Mechanisms.
Funder
National Health and Medical Research Council
Funding Amount
$456,189.00
Summary
Nerve injuries are in most cases untreatable, leaving patients with high level of disabilities for the rest of their life. Understanding the molecular mechanism regulating nerve regeneration is critical to develop new drugs and design innovative therapies. We discovered molecules that mediates axonal repair by favouring the stitching together of the two separated fragments of an axon. We aim to study how they functions to possibly exploit a similar mechanism of repair for human injuries.
Understanding Axonal Fusion: An Alternative Mechanism To Repair Injured Axons.
Funder
National Health and Medical Research Council
Funding Amount
$648,447.00
Summary
Being able to repair an injured nerve by stitching the two damages sections back together is an incredible challenge in neurosurgery, and a highly desired outcome for the surgeon as well as for the patient suffering a spinal cord or peripheral injury. We have discovered molecules that mediate nerve repair by favouring the reconnection of the two separated fragments. We will study how they function, and if they can be applied to repair injured mammalian neurons.
Identification And Study Of Novel Conserved Molecule With An Axonal Protective Function
Funder
National Health and Medical Research Council
Funding Amount
$625,005.00
Summary
Axonal degeneration is a common feature of a number of neurodegenerative conditions, such as motor neuron, Parkinson’s, Alzheimer’s and Huntington’s diseases. However, the genetic causes that regulate this biological event are poorly understood. We have identified a novel, conserved axonal protective molecule. We will study how it functions, and if it can be exploited to protect diseased neurons.
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
G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, elec ....G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, electrical and fluorescence techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in integrating diverse extracellular stimuli and neuronal excitablility in the peripheral nervous system.Read moreRead less
Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thor ....Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thorough characterisation of a novel pathway that is potentially crucial in the development, homeostasis and regeneration of the nervous system. Disruption of normal function of this system may underlie the hyperexcitability observed in mannu neurodegenerative conditions.Read moreRead less
Understanding The Role Of TDP-43 In Motor Neuron Disease.
Funder
National Health and Medical Research Council
Funding Amount
$654,091.00
Summary
Motor neuron disease (MND) is a fatal neurodegenerative disease with no cure. The cause of MND is poorly understood but new research has shown that defects in TDP-43, an RNA binding protein involved in gene regulation, can lead to the disease. This project is aimed at discovering the molecular mechanisms of TDP-43 function, which will improve the understanding of the disease and aid in the development of new therapies.
Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds ....Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds of fusion. This recycling process ensures that neurons communicate efficiently, however the underpinning mechanism is unknown. This project aims to use a recently developed single synaptic vesicle super-resolution tracking method to establish how Myosin-VI and Synapsin-IIa orchestrate this recycling in central and peripheral neurons. It will explain how neurons manage to preserve their ability to communicate.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