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
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
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.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100008
Funder
Australian Research Council
Funding Amount
$347,500.00
Summary
Super Resolution Confocal Microscopy Facility. Super resolution confocal microscopy facility:
This project aims to establish a super-resolution confocal microscopy facility with unrivalled resolution, sensitivity and speed. The widespread application of super-resolution microscopy has so far been limited because of the special sample preparation and technical skills required. The project aims to provide us with the ability to image thicker samples, such as animal and plant tissue, without these ....Super Resolution Confocal Microscopy Facility. Super resolution confocal microscopy facility:
This project aims to establish a super-resolution confocal microscopy facility with unrivalled resolution, sensitivity and speed. The widespread application of super-resolution microscopy has so far been limited because of the special sample preparation and technical skills required. The project aims to provide us with the ability to image thicker samples, such as animal and plant tissue, without these limitations. This would enable us to capture three-dimensional data at both the cellular and tissue level, providing researchers with a level of detail never before seen. The facility may create new knowledge in life science, including visual neuroscience, developmental neurobiology, plant growth, stem cell regeneration, the role of trace metals in physiology, and vaccine and drug development.Read moreRead less
A toxic cycle of inflammation and iron in the ageing brain. This project investigates why our brain cells gradually die as we grow older. We believe that infections and inflammation in other parts of the body cause iron to accumulate in the brain and become toxic. Iron supplements and ageing may make this situation worse. The results of this study could lead to new treatments for memory loss and dementia.
Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels. Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This p ....Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels. Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This project aims to determine the basis of ion permeation and selectivity in the channels and explain the mechanisms of action for a number of common drugs. This will provide a foundation for future drug development to target specific channels for improved treatment of epilepsy, chronic pain and arrythmias. Read moreRead less
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less
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.
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.
Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.