Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453295
Funder
Australian Research Council
Funding Amount
$369,697.00
Summary
NMR cryosystem for structural and functional biology. State-of-the-art hardware is requested for the 600-MHz NMR spectrometers situated at University of Sydney and UNSW. A cryosystem installed at USyd. will provide a massive boost in productivity and will allow projects previously inaccessible due to excessive turn-around times, or sensitivity or solubility problems to become tractable. This system will provide new opportunities to researchers from USyd., UNSW and ANU, but will restrict the ver ....NMR cryosystem for structural and functional biology. State-of-the-art hardware is requested for the 600-MHz NMR spectrometers situated at University of Sydney and UNSW. A cryosystem installed at USyd. will provide a massive boost in productivity and will allow projects previously inaccessible due to excessive turn-around times, or sensitivity or solubility problems to become tractable. This system will provide new opportunities to researchers from USyd., UNSW and ANU, but will restrict the versatility of the USyd. instrument. The installation of a TBI probe at UNSW will counter this, and provide a REAL network of NMR instruments across NSW and the ACT.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
How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Ke ....How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Key to this process are membrane dynamics during synaptic vesicle retrieval, but the precise underlying mechanisms are not well understood. The intended outcome of this project is insights into the molecular mechanisms of synaptic transmission, the fundamental process of brain function, increasing understanding of physiological processes such as muscle movement, vision, hearing, touch, learning and memory.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100078
Funder
Australian Research Council
Funding Amount
$800,000.00
Summary
Live molecular imaging using super resolution microscopy, two photon and spinning disk confocal microscopy. With recent developments of super-resolution microscopy it is now feasible to image single molecules within the cellular environment in living cells. Such insight is key to understanding basic biological interactions that govern the wiring of our brain, communications between cells and neurons and cell-cell adhesion.
Nuclear functions of the microtubule-associated protein tau. The important neuronal protein, tau, has cellular functions that go far beyond its established role in stabilising microtubules. This project will determine which tau species are nuclearly localised, what the consequences are for nuclear functions, and how phosphorylation regulates this localisation.
Investigating the neuroprotective actions of metallo-complexes. Metal-based drugs offer an exciting new approach to treatment of neurodegeneration. However, little is known about how cells metabolise these drugs: information that is critical for further drug development. This project will determine how metal-based drugs are metabolized by neuronal cells and how this may result in therapeutic benefit.
The role of tropomyosin in coordinated neurite branching. This project will explore how nerve cells generate a highly branched network of cell processes which allows all higher functions of the nervous system. We previously discovered the central role of a component of the cell architecture in determining the branching pattern and in this project expect to reveal the molecular basis for its function.
Targeting brain lipid homeostasis to treat Alzheimer's disease. Dementia affects approximately 250,000 people in Australia at an estimated cost (in 2002) of $6.6 billion per annum. The major cause of dementia (accounting for approximately 70% of all cases) is Alzheimer's disease (AD); a progressive neurodegenerative illness for which there is no curative or disease-stalling treatment. Due to increases in life expectancy, the incidence of AD is predicted to triple by 2050 unless disease-modifying ....Targeting brain lipid homeostasis to treat Alzheimer's disease. Dementia affects approximately 250,000 people in Australia at an estimated cost (in 2002) of $6.6 billion per annum. The major cause of dementia (accounting for approximately 70% of all cases) is Alzheimer's disease (AD); a progressive neurodegenerative illness for which there is no curative or disease-stalling treatment. Due to increases in life expectancy, the incidence of AD is predicted to triple by 2050 unless disease-modifying treatments are developed. This research program will provide novel realistic pharmaceutical approaches to treat AD. Even if the onset of AD could be delayed by a few years the personal and financial benefits would be enormous. The potential for this research to generate commercially viable Australian intellectual property is also significant.Read moreRead less
The role of LIM Kinase 1 in neurons. The aim of this project is to study LIM domain kinase 1 in neuronal function, using cell and mouse models. Unrestricted brain function is essential to one’s wellbeing and the ability to perform normally. Critically contributing to the function of neurons is a cytoskeleton which maintains morphology and function. However, molecular mechanisms underlying cytoskeletal dynamics are poorly understood. LIM domain kinase 1, a key regulator of the actin cytoskeleton ....The role of LIM Kinase 1 in neurons. The aim of this project is to study LIM domain kinase 1 in neuronal function, using cell and mouse models. Unrestricted brain function is essential to one’s wellbeing and the ability to perform normally. Critically contributing to the function of neurons is a cytoskeleton which maintains morphology and function. However, molecular mechanisms underlying cytoskeletal dynamics are poorly understood. LIM domain kinase 1, a key regulator of the actin cytoskeleton decreased with age and its loss associated with deficits in memory and neuronal morphology. This project could reveal fundamental processes regulating and maintaining brain function.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