Wiring the gut's nervous system: formation and maturation of synapses. This project aims to determine how nerve circuits controlling intestinal functions develop; specifically how communication between specific nerve cells is established once they appear in the embryonic gut. It will fill a major hole in existing knowledge of mechanisms regulating the development of normal digestive behaviours.
The role of actin in driving bulk endocytosis in neurons and neurosecretory cells. Synaptic release of neurotransmitter is essential for neuronal communication. Following fusion, synaptic vesicle membrane is incorporated into the plasma membrane and retrieved by endocytosis to recover both lipids and essential vesicular proteins. The project will characterise how the actin cytoskeleton perform this function.
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 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
Visualising neuron-glia interactions in the injured central nervous system. The adult brain and spinal cord recovery poorly from injury. Attempts to overcome this problem include methods to promote the intrinsic regenerative capacity of injured neurons, and modulating the inhibitory extracellular environment to become permissive to regeneration. The goal of this project is to investigate an endogenous regenerative mechanism in the injured brain. This project will use the latest, cutting-edge mic ....Visualising neuron-glia interactions in the injured central nervous system. The adult brain and spinal cord recovery poorly from injury. Attempts to overcome this problem include methods to promote the intrinsic regenerative capacity of injured neurons, and modulating the inhibitory extracellular environment to become permissive to regeneration. The goal of this project is to investigate an endogenous regenerative mechanism in the injured brain. This project will use the latest, cutting-edge microscopy techniques to visualise whether the endogenous astrocyte protein metallothionein can promote regeneration in the injured nervous system of living zebrafish. The successful outcomes of this project will provide significant insight into understanding how the brain responds to injury.Read moreRead less
I am a lab-based neurochemist-cell biologist with expertise in protein chemistry and pharmacology. My research focuses on the dynamin family of proteins in the endocytosis of synaptic vesicles and in the molecular mechanisms of synaptic transmission in th
Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The stud ....Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The study of this transport process will be important for understanding disorders like epilepsy and other disorders affecting neuronal excitability.Read moreRead less
Differential Regulation Of Two Modes Of Exocytosis By Protein Phosphatases
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
The release of signals from nerve endings (exocytosis) is of fundamental importance to nervous system function. The recent recognition that nerve cells can release transmitter by at least two distinct modes of exocytosis has led to the need for a deeper understanding of the mechanisms that regulate exocytosis. Our identification of the key role played by two enzymes, PP2A and PP2B, represents a major insight into the molecular mechansisms regulating this process. The experiments will lead to the ....The release of signals from nerve endings (exocytosis) is of fundamental importance to nervous system function. The recent recognition that nerve cells can release transmitter by at least two distinct modes of exocytosis has led to the need for a deeper understanding of the mechanisms that regulate exocytosis. Our identification of the key role played by two enzymes, PP2A and PP2B, represents a major insight into the molecular mechansisms regulating this process. The experiments will lead to the identification of how PP2A and PP2B are regulated at the molecular level and the targets that are important in the control of exocytosis. The project will also develop new tools to specifically manipulate the two modes of exocytosis in order to understand their contribution to normal and pathological neurotransmission. Strong stimulation of exocytosis is associated with learning and memory in normal brain and neuronal damage under certain pathological conditions. Since switching from 1 mode of exocytosis to another is also induced by strong stimulation, an understanding of the molecular mechanisms that control the different modes of exocytosis may eventually lead to clinical applications.Read moreRead less
The Effect Of Alteration Of Glucose Use On Brain Function
Funder
National Health and Medical Research Council
Funding Amount
$131,731.00
Summary
Glucose has long been accepted as the mandatory fuel for the brain although it is not fully understood why this is so. Impairment of the glucose supply to the brain results in impairment in brain functions, coma and ultimately death. As a result the body possesses rigid regulatory systems to maintain blood glucose levels within set limits. In certain conditions where blood glucose levels frequently drop below normal, the brain compensates by increasing the uptake of glucose into the brain thus k ....Glucose has long been accepted as the mandatory fuel for the brain although it is not fully understood why this is so. Impairment of the glucose supply to the brain results in impairment in brain functions, coma and ultimately death. As a result the body possesses rigid regulatory systems to maintain blood glucose levels within set limits. In certain conditions where blood glucose levels frequently drop below normal, the brain compensates by increasing the uptake of glucose into the brain thus keeping the glucose supply normal despite lower than normal blood glucose concentrations. In these conditions, which include diabetic hypoglycaemia unawareness, anorexia and starvation, the normal hormonal systems warning of low blood glucose are bypassed. However, despite normal glucose supply to the brain, the performance of the brain is still adversely affected. The electrical activity of the brain changes, reaction times slow, and vigilance is decreased. This implies that, despite the brain having a normal supply of glucose, the glucose is being used differently and that these differences affect the functional performance of the brain. The AIMS of this study are to determine: 1. How does the use of glucose vary in the hypoglycaemia unawareness state? 2. How do these variations effect the performance of the brain? The SIGNIFICANCE of this work lies in 1. Increasing our understanding of the role of glucose in the brain, 2. Increasing our understanding of how the brain works, and, 3. Increasing our understanding of why cognitive impairment occurs in disorders such as diabetes, anorexia and starvation and whether this impairment is reversible. 4. Developing application of a relatively new technique, functional magnetic resonance spectroscopy, for use study of biochemical and cognitive brain disorders.Read moreRead less