Neogenin Regulates Progenitor Division And Interneuron Migration In The Developing Forebrain
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
In humans, mutations in genes controlling the production of new neurons in the embryonic brain result in severe disruption of the adult cortex. This project tests the hypothesis that one cell surface molecule, Neogenin, regulates the birth of new neurons and their subsequent travels through the developing brain to form the neocortex. The outcome of these studies will provide fundamental insights into the aberrant processes that underlie human mental retardation, epilepsy, dyslexia and autism.
Prof Paxinos ‘s work is involved in understanding brain organisation and function through the fusion of the fields of molecular genetics, comparative and developmental neuroanatomy and Neuro informatics
Molecular Determinants Of Inhibitory Synaptic Function Studied Using Mutant And Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Communication between nerve cells is the key to effective brain function and when disturbed, pathological states such as epilepsy, schizophrenia, fear and anxiety, spasticity and motor disorders ensue. This project is based on new data which suggests that the site of this communication, called the synapse, is a much more dynamic structure than previously thought. Based on our work to date, where we have demonstrated the recruitment of selected classes of neurotransmitter receptors into synapses, ....Communication between nerve cells is the key to effective brain function and when disturbed, pathological states such as epilepsy, schizophrenia, fear and anxiety, spasticity and motor disorders ensue. This project is based on new data which suggests that the site of this communication, called the synapse, is a much more dynamic structure than previously thought. Based on our work to date, where we have demonstrated the recruitment of selected classes of neurotransmitter receptors into synapses, our aim is to use a range of naturally occuring mice mutants, as well as transgenic mice to modulate the receptor levels and so to examine the role of synaptic function and synaptic dynamics. The outcomes of this project will provide fundamental new knnowledge aimed at understanding how communication in the nervous system works and may suggest ways in which modulation of this information flow could be used to treat disorders of brain function.Read moreRead less
Novel Substance P Receptors On Autonomic And Sensory Neurons Regulating The Viscera
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
Potentially harmful stimulation of the skin or the internal organs activates sensory nerves that send signals to the brain. These events often are perceived as painful. One chemical messenger transmitting these signals first to the spinal cord, and then to the brain, is a neuropeptide called substance P. During many chronic inflammatory conditions, such as inflammation of the bowel, these signalling pathways are sensitised so that stimuli that previously were not painful now are perceived as pai ....Potentially harmful stimulation of the skin or the internal organs activates sensory nerves that send signals to the brain. These events often are perceived as painful. One chemical messenger transmitting these signals first to the spinal cord, and then to the brain, is a neuropeptide called substance P. During many chronic inflammatory conditions, such as inflammation of the bowel, these signalling pathways are sensitised so that stimuli that previously were not painful now are perceived as painful. This sensitisation has several different causes. One contributing factor seems to be related to a change in the receptor molecules that recognise substance P. Last year we discovered a new type of receptor for substance P, that is prominent in the nerve pathways between the gut and the spinal cord. This novel receptor has important characteristics that are different from the classical substance P receptor. However, we are still largely ignorant about how substance P interacts with these new receptors to modify the activity of nerve cells in sensory pathways. Indeed, we propose that these new receptors are likely to make a significant contribution to the sensitisation that occurs in inflammation. We will use a combination of sophisticated cellular and molecular techniques to study the way in which substance P acts on these novel receptors in nerves regulating the visceral organs. Our results are likely to make a significant contribution to the development and interpretation of rational new therapies for treating chronic diseases of the gastrointestinal tract, such as inflammatory bowel disease (IBD). Our studies will reveal signalling mechanisms that also are likely to be used by substance P more widely in the nervous system, that are relevant to other inflammatory conditions like arthritis, and even some forms of depression.Read moreRead less
Roles Of Brain-derived Neurotrophic Factor In Plasticity Of Injured Sensory Neurons
Funder
National Health and Medical Research Council
Funding Amount
$461,443.00
Summary
The fundamental problem of how nerve cells respond to a nerve injury has long been studied by neuroscientists and clinicians. After a nerve injury outside the brain or spinal cord, ie, in the periphery, some sensory nerve cells die, some regenerate to reconnect to their targets, and some sprout to make abnormal connections. Recent evidence from our lab and others indicates that the nerve sprouting is linked to chronic pain experienced by nerve-injury patients. However, how these changes occur st ....The fundamental problem of how nerve cells respond to a nerve injury has long been studied by neuroscientists and clinicians. After a nerve injury outside the brain or spinal cord, ie, in the periphery, some sensory nerve cells die, some regenerate to reconnect to their targets, and some sprout to make abnormal connections. Recent evidence from our lab and others indicates that the nerve sprouting is linked to chronic pain experienced by nerve-injury patients. However, how these changes occur still remains largely unknown. Our recent studies showed that growth factors, particularly brain-derived neurotrophic factor (BDNF) which is made by the sensory nerve cells, may play important roles in mediating these changes. This proposed project, directly evolved from our recent exciting findings, aims to further examine roles and action mechanisms of BDNF and its relatives in regulating the responses of sensory nerve cells to a nerve injury. We propose that after an injury, BDNF promotes survival of some nerve cells, enhances sensory nerve regeneration in both periphery and spinal cord, and also mediates abnormal nerve sprouting and is involved in neuropathic pain. With strong expertise and powerful tools in hand, we have designed a series of experiments to investigate the roles and action mechanisms of BDNF and its related molecules in these processes. Results from this project will help us understand mechanisms underlying the responses of nerve cells to a nerve injury, and should provide much needed information which would help in designing new methods for enhancing nerve cell survival and nerve regeneration as well as for inhibiting nerve injury-induced chronic pain in nerve-injury patients.Read moreRead less
Targeting the host lipid environment to disrupt malaria transmission. This project aims to characterise host molecules (in particular lipids) that are crucial for the transition of malaria parasites from one host to another. Malaria parasites encounter different environments upon their transition from human to the mosquito host. This project expects to generate new knowledge on physiological changes that are triggered by particular differences in micronutrient abundance that allow the parasites ....Targeting the host lipid environment to disrupt malaria transmission. This project aims to characterise host molecules (in particular lipids) that are crucial for the transition of malaria parasites from one host to another. Malaria parasites encounter different environments upon their transition from human to the mosquito host. This project expects to generate new knowledge on physiological changes that are triggered by particular differences in micronutrient abundance that allow the parasites to survive in the new host. Anticipated outcomes include the identification of new intervention strategies and improved transmission model systems for vector-borne diseases. This gained knowledge could provide benefits to future biomedical applications by informing diagnostics or treatment of lipid associated diseases.Read moreRead less
The Role Of Neuronal Hyper-excitability In An Animal Model Of Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$558,170.00
Summary
Every day at least one person in Australia dies of the fatal and untreatable adult neurodegenerative disease of amyotrophic lateral sclerosis (motor neuron disease). This research examines the factors driving early increases in neural activity which may lead to the loss of upper and lower motor neurons in adulthood. The use of new methods to suppress production of specific proteins causing increased neural activity may lead to novel treatments for this disease.
Regulation Of P75 Death Signalling: How Neurotransmitter- And Neurotrophic- Signals Determine Cell Survival
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Nerve cell survival is dependent on trophic support in the form of growth factors and synaptic input, both of which promote recovery after nerve injury. The survival pathways activated by growth factors are generally well characterised, whereas survival signals activated by synaptic activity are largely unexplored. This proposal aims to discover how synaptic activity prevents nerve cell death by looking at how synaptic activity inhibits the processes active in dying nerve cells.