A Novel Mechanism For The Maintenance Of Catecholamine Synthesis
Funder
National Health and Medical Research Council
Funding Amount
$356,250.00
Summary
Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the dru ....Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the drugs all affect the catecholamine systems. Tyrosine hydroxylase controls catecholamine synthesis and it is activated in both the acute and adaptive phases of the stress response in order to replace catecholamines that have been secreted. Tyrosine hydroxylase is activated by protein phosphorylation in the acute phase and by the synthesis of new tyrosine hydroxylase in the adaptive phase. We have now discovered an additional and novel phase that we refer to as sustained tyrosine hydroxylase activation. This phase spans at least the period between the acute (mins) and adaptive phases (days). It involves the sustained phosphorylation of tyrosine hydroxylase and its mechanism appears to differ from the other two phases. In this project we will answer three questions. Does sustained tyrosine hydroxylase activation: 1 Occur in response to many stimuli and in many catecholamine cell types? 2 Occur by a single mechanism, different to the other phases, in all circumstances? 3 Play a role in the control of blood pressure and depression? This project will provide fundamental data about the mechanisms and consequences of sustained tyrosine hydroxylase activation, which is a part of the stress response not previously discovered. The data may impact on the way we design drugs to control stress responses, including antidepressants and antihypertensives.Read moreRead less
Transcriptional control of neural stem cell differentiation during development and disease. Understanding the molecular mechanisms that control how neural stem cells differentiate is critical to provide potential therapeutic treatment for neurodegenerative diseases and for brain cancer. This project will aim to discover, using an animal model system, the genes and molecules regulating these key biological processes.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100074
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genet ....Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genetic and acquired disorders across the life-span. Remote viewing and analysis capabilities will help overcome the 'tyranny of distance', increasing national access to the facility. Repositories of digitised images will increase the availability of valuable research material to other Australian and international researchers.Read moreRead less
Cellular and Neurochemical Basis of Drug Addiction. Addiction to the major drugs of abuse, including heroin, amphetamines, cocaine, nicotine and alcohol damage the lives and cause premature death of more than 20% of Australians. Addiction produces long-term disruption of brain processes that lead to loss of control over urges to consume drugs and persistent cycles of relapse to drug taking. This research will apply new neurochemical approaches to discover mechanisms of disrupted brain function t ....Cellular and Neurochemical Basis of Drug Addiction. Addiction to the major drugs of abuse, including heroin, amphetamines, cocaine, nicotine and alcohol damage the lives and cause premature death of more than 20% of Australians. Addiction produces long-term disruption of brain processes that lead to loss of control over urges to consume drugs and persistent cycles of relapse to drug taking. This research will apply new neurochemical approaches to discover mechanisms of disrupted brain function that occur during development of addiction and relapse that are critical for development of better strategies to treat the disorder. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453630
Funder
Australian Research Council
Funding Amount
$274,692.00
Summary
High-Speed Confocal Microscope Live Cell Recording System. The high-speed confocal microscope live cell recording system we are establishing represents new generation equipment. It allows quality imaging of selected subcellular regions of live cells combined with simultaneous electrophysiological recording at rates and sensitivity hitherto not possible. This equipment provides a window of opportunity for major research advances in that it allows real-time two and three-dimensional imaging of fun ....High-Speed Confocal Microscope Live Cell Recording System. The high-speed confocal microscope live cell recording system we are establishing represents new generation equipment. It allows quality imaging of selected subcellular regions of live cells combined with simultaneous electrophysiological recording at rates and sensitivity hitherto not possible. This equipment provides a window of opportunity for major research advances in that it allows real-time two and three-dimensional imaging of fundamental cellular activities that previously could not be viewed. It will allow major advances in priority health-related research and will provide an ideal research tool to introduce young scientists and students to cutting edge research.Read moreRead less
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.
Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly inc ....Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly increase our understanding of how the development of this critical aspect of organismal function is orchestrated during development. This project will also develop bioinformatics tools with broad utility within the biosciences field and enhance the capacity for interdisciplinary international collaborations.Read moreRead less
Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also mi ....Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. The planned data are likely to be relevant to other cell populations that also populate the areas through which they migrate, including neural crest-derived melanocytes and Schwann cell precursors.Read moreRead less
Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aime ....Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aimed at developing treatments for diseases like chronic constipation and irritable bowel syndrome. It will also contribute to the growing knowledge about how epigenetic factors can modify genetically programmed development within the nervous system.Read moreRead less
Cell cycle and enteric neuron and glial differentiation. Enteric neurons arise from a very small starting population of precursor (neural crest) cells, most of which emigrate from the hindbrain, and colonise the developing gut. Over a protracted period of time the precursors proliferate and differentiate into glia and many different types of neurons. Cell cycle exit is a critical event in the development of many neuron types, largely because the time at which cells exit from the cell cycle lim ....Cell cycle and enteric neuron and glial differentiation. Enteric neurons arise from a very small starting population of precursor (neural crest) cells, most of which emigrate from the hindbrain, and colonise the developing gut. Over a protracted period of time the precursors proliferate and differentiate into glia and many different types of neurons. Cell cycle exit is a critical event in the development of many neuron types, largely because the time at which cells exit from the cell cycle limits the number of neurons that will be generated. We will determine whether exit from the cell cycle contributes to the differentiation and specification of enteric neurons and glia.Read moreRead less