Phosphatase Regulators Mediate Long-term Changes In Presynaptic Terminals
Funder
National Health and Medical Research Council
Funding Amount
$984,163.00
Summary
The strength of communication between each nerve cell in the brain depends on how active that nerve cell has been. This enables the brain to be adaptable and is a way for the brain to set up circuits that underlie how we learn and remember. More or less release of chemical messengers (neurotransmitters) into nerve cell junctions changes the strength of nerve cell communication. We have discovered a new chemical signalling pathway controlling neurotransmitter release.
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
Molecular Mechanisms Of Dynamin-mediated Endocytosis In Nerve Terminals
Funder
National Health and Medical Research Council
Funding Amount
$1,033,626.00
Summary
Neurons communicate by neurotransmitter release from synaptic vesicles stored in nerve endings. There is a finite vesicle number, so they are recycled (endocytosis) by the protein dynamin. Our aim is to reveal how new vesicles are produced when the brain is under very high activity, to better understand diseases of the synapse like epilepsy. We propose that two forms of the dynamin gene mediate this process, only under conditions of high neuronal firing, such as occurs during a seizure.
Inhibitory Signalling Switches Define The Machinery Of Synaptic Vesicle Endocytosis
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
The nerve cells in our brains are in constant communication to sustain life. Communication involves one nerve cell responding to electrical stimulation by releasing chemical messengers, from vesicles, onto the next cell. Our research focuses on the mechanism of recycling of vesicles. Targeting this mechanism is a way to gain fundamental knowledge of how to intervene medically when communication fails, or when communication needs to be dampened, in neurological diseases.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100036
Funder
Australian Research Council
Funding Amount
$470,000.00
Summary
A protein molecular interaction and localization facility. This proposal will address a major gap in our mass spectrometry capabilities and aid in our understanding of protein interactions and tissue distribution in areas such as neuroscience, microbiology, immunology, and botany, as well as enhance our understanding of fundamental gas phase chemistry of protein molecules. It brings together a highly successful multidisciplinary team of high-profile researchers with a track record of collaborati ....A protein molecular interaction and localization facility. This proposal will address a major gap in our mass spectrometry capabilities and aid in our understanding of protein interactions and tissue distribution in areas such as neuroscience, microbiology, immunology, and botany, as well as enhance our understanding of fundamental gas phase chemistry of protein molecules. It brings together a highly successful multidisciplinary team of high-profile researchers with a track record of collaboration and delivering outcomes from shared facilities. In addition to these key scientific outcomes this project will also facilitate the training of several new personnel in a skill area for which there is a critical shortage (mass spectrometry) and promote true cross-disciplinary skills.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
Phosphorylation Of Synaptic Vesicle Glycoprotein 2 (SV2) Regulates Endocytosis Of Synaptotagmin For Synaptic Transmission
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Antiepileptic drugs typically target ion transporters or neurotransmitter receptors. Synaptic vesicle glycoprotein 2 (SV2) is a rare example of a synaptic vesicle recycling protein that is the target of an antiepileptic drug. It also binds botulinum and tetanus neurotoxins. We discovered SV2 contains activity-dependent signalling molecules. Charactersation of these molecules and will allow a deeper understanding of the molecular basis for its role in epilepsy and toxin action.
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
Mechanisms Of Synaptic Vesicle Endocytosis Revealed By Its Regulatory Phosphoproteome
Funder
National Health and Medical Research Council
Funding Amount
$545,216.00
Summary
The nerve cells in our brains are in constant communication to sustain life. Communication involves electrical stimulation of one nerve cell which then responds by releasing chemical messengers, from vesicles, onto the next cell. Our research focuses on the mechanism of recycling of vesicles. Targeting this mechanism is a way to gain fundamental knowledge of how to intervene medically when communication fails, or when communication needs to be dampened, such as in some neurological diseases.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100008
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
Laser microdissection microscopy system for cell and development biology. The University of Newcastle has invested heavily in its biological and life sciences to create a research nexus focusing on national research priorities in biotechnology and environmental protection. The live cell laser microdissection platform will be utilised by scientists researching such strategically important areas as developmental biology, intracellular signalling cascades, cell cycle dynamics, plant development and ....Laser microdissection microscopy system for cell and development biology. The University of Newcastle has invested heavily in its biological and life sciences to create a research nexus focusing on national research priorities in biotechnology and environmental protection. The live cell laser microdissection platform will be utilised by scientists researching such strategically important areas as developmental biology, intracellular signalling cascades, cell cycle dynamics, plant development and microbiology. Moreover, this component of the University's research portfolio plays a major role in the postgraduate training of young Australian scientists who will, in turn, fuel future developments in both the life sciences and biotechnology industries.Read moreRead less