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
A New Function For An Old Enzyme: Src Protein Kinase Directs Excitotoxic Neuronal Death In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$513,975.00
Summary
In our previous investigation of how brain cells die in patients suffering from stroke, we found that stroke causes aberrant activation of an enzyme called Src in the affected brain cells. Furthermore, this aberrantly activated Src directs the brain cells to undergo cell death. Our proposal, which aims to decipher this neurotoxic mechanism of the aberrantly activated Src will benefit development of new therapeutic strategies to reduce brain damage in stroke patients.
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.
Single cell imaging of trace elements by laser ablation - inductively coupled plasma - mass spectrometry. The precise mechanism of how many diseases function on the cellular level is not well understood. Trace elements are important to normal cellular function and have the potential to cause significant damage if delicate levels are disturbed. This project will introduce a new, cost-effective alternative to the synchrotron for mapping of trace elements in single cells. This breakthrough science ....Single cell imaging of trace elements by laser ablation - inductively coupled plasma - mass spectrometry. The precise mechanism of how many diseases function on the cellular level is not well understood. Trace elements are important to normal cellular function and have the potential to cause significant damage if delicate levels are disturbed. This project will introduce a new, cost-effective alternative to the synchrotron for mapping of trace elements in single cells. This breakthrough science will transform a common analytical instrument into a powerful new tool for probing the cellular mechanisms of chronic illness. This frontier technology will help determine the role of trace metals in the development of neurodegenerative disease.Read moreRead less
The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes ....The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes to characterise the structure and function of a newly identified copper-dependent form of cell enzyme which could be involved in amplifying ubiquitin-tagged protein breakdown. Copper is essential for life in all domains. Identifying copper as a major regulator in protein clearance is important in understanding this fundamental biological machinery.Read moreRead less
Functional studies on a novel, brain-specific, Golgi ATP-binding protein in membrane trafficking. In cells specialised for communication such as neurones, protein transport constitutes a large part of total cellular activity. A primary pathway in protein transport is trafficking from the Golgi apparatus to the cell membrane; materials destined for the cell membrane and secretion are sorted, packed and transported from the Golgi apparatus. However, the mechanisms underlying these processes at the ....Functional studies on a novel, brain-specific, Golgi ATP-binding protein in membrane trafficking. In cells specialised for communication such as neurones, protein transport constitutes a large part of total cellular activity. A primary pathway in protein transport is trafficking from the Golgi apparatus to the cell membrane; materials destined for the cell membrane and secretion are sorted, packed and transported from the Golgi apparatus. However, the mechanisms underlying these processes at the Golgi remain largely unknown. We have recently cloned a novel ATP-binding protein specifically expressed at the Golgi apparatus in human brain, and hypothesise that this protein regulates Golgi protein trafficking by interacting with two other molecules, dynamin and calcium, during cell secretion.Read moreRead less
The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will presen ....The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will present a medical and economic challenge demanding novel and powerful science. This research will lead both to deeper understanding of the basic mechanisms underlying such disorders and to tools for designing new and effective treatments.
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Investigating the intercellular trafficking of proteins and RNA and its relevance to neurodegenerative diseases. Alzheimer's and prion diseases are neurodegenerative disorders associated with protein misfolding. This project brings together similar features of these diseases using novel cell- and animal-based studies to develop a greater understanding of the molecular basis of these disorders.
Novel modes of signalling of serotonin 5-HT2c receptors. This project focuses on a special family of receptor proteins that mediate the actions of the neurochemical, serotonin (5HT), in the human brain. These serotonin receptors are major targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and control of appetite. Despite the important role of serotonin receptors in health and disease, the mechanism of action of many drugs acting on these receptors ....Novel modes of signalling of serotonin 5-HT2c receptors. This project focuses on a special family of receptor proteins that mediate the actions of the neurochemical, serotonin (5HT), in the human brain. These serotonin receptors are major targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and control of appetite. Despite the important role of serotonin receptors in health and disease, the mechanism of action of many drugs acting on these receptors remains unknown. Our project will specifically investigate novel molecular mechanisms associated with serotonin receptor activity that may prove vital in understanding mechanisms of psychiatric illnesses, and how many psychiatric medicines actually work.Read moreRead less
Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will appl ....Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will applications of stem cell biology, and will stimulate clinical researchers to investigate the therapeutic potential of cell derived from NS cells.Read moreRead less