Astrocyte-Neuron Communication: Unravelling The Role Of Astrocytes In The Modulation Of Neuronal Circuits
Funder
National Health and Medical Research Council
Funding Amount
$403,064.00
Summary
Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neur ....Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neurodegenerative states (e.g. Alzheimer's disease, Parkinson's disease, and multiple sclerosis). Many of these diseases are associated with a pathological astrocyte process known as 'reactivity'. This process remains enigmatic, resulting in so-called reactive gliosis, a reaction characterized by changes in gene expression, cell enlargement and changes in cell shape, and, in some cases, cell division. Most of the research on astrocyte reactivity has focused on the impairment of astrocyte metabolic activities. Comparatively little is known about the effect of reactive gliosis on so called 'newer' astrocyte roles such as their ability to interact with each other and nearby neurons using exocytosis of gliotransmitters (GTs: glutamate and ATP) and neurotrophic factors (NTFs: glial and brain derived neurotrophic factors). This project will both further investigate the normal mechanisms of astrocyte-neuron communication, and examine the effects of astrocyte reactivity on these mechanisms. The aim is to identify possible therapeutic targets to ameliorate the detrimental affects of neurodegeneration.Read moreRead less
Assessing The Role Of The N-terminus Of The Prion Protein, Emphasising Constitutive Cleavage, In Normal Function And Pathogenesis, As Well As Defining The Relationship Between Intensity Of Surveillance And Sporadic CJD Incidence.
Funder
National Health and Medical Research Council
Funding Amount
$387,469.00
Summary
As a neurologist undertaking research into prion diseases over an extended period, I have been able to lead and participate in many projects that have made significant contributions, such as validation of new diagnostic tests for Creutzfeldt-Jakob disease (CJD), assessment of potential therapeutics, provide insights into the normal function of the prion protein and the underlying pathways causing cellular damage and determine the real significance of apparent clusters of sporadic CJD.
The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themse ....The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themselves and information that could help in the development of new and more effective drugs, and biomarkers to assist in the prediction of prognosis. Such advances would decrease the economic impact of these diseases and improve quality of life for those affected.Read moreRead less
New tools to activate and silence neural circuits. Many neurological disorders occur as a result of neuron cell death that is initiated by excessive levels of excitatory activity in central nervous system neurons. This project will develop and validate a new treatment for these disorders that involves silencing excessive neuronal activity using a safe, commonly prescribed drug.
Gene-environment interactions mediating experience-dependent plasticity in the healthy and diseased brain. The aim of this project is to understand how genes and environment combine to affect susceptibility to various brain disorders, using models of human diseases and manipulating environmental factors such as mental and physical activity. The project's focus is on neurological and psychiatric disorders, including Huntington's disease, depression, schizophrenia and autism.
Pontine control of adaptive breathing behaviour in health and disease. This project will develop an understanding of the fundamental brain mechanisms associated with adaptive breathing during behaviour such as speech or swallowing. Adaptive breathing is impaired in lung disease, dementia and autism. This project will provide new insight to global brain function and treatment of central respiratory disorder.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100029
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
High Resolution PET-CT for Small Animal Molecular and Anatomical Imaging. This project will integrate a next generation small animal PET-CT instrument into the Sydney Imaging multi-modality imaging ecosystem. PET-CT enables the investigation of molecular function and anatomical structure in complex living organisms. This platform will enable research as diverse as the development and in-vivo characterisation of new chemical probes and nanoparticles that bind to specific protein targets in the bo ....High Resolution PET-CT for Small Animal Molecular and Anatomical Imaging. This project will integrate a next generation small animal PET-CT instrument into the Sydney Imaging multi-modality imaging ecosystem. PET-CT enables the investigation of molecular function and anatomical structure in complex living organisms. This platform will enable research as diverse as the development and in-vivo characterisation of new chemical probes and nanoparticles that bind to specific protein targets in the body, investigating mechanisms of brain plasticity in predictive learning, understanding the molecular pathways involved in neurodegeneration and cancer, developing novel methods for multi-modal image analysis, and developing and validating new radiation detectors for the next generation of imaging technology.Read moreRead less
The role of P2X7 and P2X4 receptor mediated innate phagocytosis in pathogenesis and treatment of neurodegenerative diseases. This project will identify how inherited variation in two proteins of the brain can accelerate the removal of neurones and predispose to a range of neurodegenerative diseases. Knowledge of the biological basis of this finding will allow a search for new compounds which will slow and protect against this form of neurodegeneration.
Physiology of tau protein: a novel role in scaffolding and intracellular distribution. Understanding brain function remains a challenge. This project will study the normal role of the Alzheimer's disease-related protein tau in brain function during ageing. This will significantly enhance current understanding of brain function.
Thalamocortical Neural Circuits In Higher Order Cognitive And Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$370,860.00
Summary
Schizophrenia, depression and dementia are devastating disorders with problems in thinking and sensory perception, but the neural circuits causing these symptoms are not known. I will use new optical and genetic tools in mice to identify the cortical and subcortical circuits required for complex touchscreen tasks, the same tasks to assess patients. Identification of neural circuits that underlie clinical symptoms will increase our understanding of these disorders and improve treatments.