Muscling in on the brain. This project investigates an enzyme that 'matures' neurotransmitters in the brain that regulate food intake, energy expenditure and blood pressure by the brain; these neurotransmitters arise from the same precursor molecule. This project will show the physiological relevance of this enzyme in obesity.
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less
Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly de ....Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly developed physiological methods together with a new acetylcholine receptor drug. We also aim to assess the suitability of mice genetically modified to be deficient in acetylcholine receptors as animal models of dopamine dysfunction related to schizophrenia and drug addiction.Read moreRead less
How appetite-suppressing brain cells maintain normal function and prevent the development of obesity. The brain plays a critical role in body weight gain by balancing appetite-inducing and appetite-suppressing signals. An imbalance in this process causes obesity and promotes diabetes. The aim of this research is to identify how appetite-suppressing brain cells maintain normal function and prevent the development of obesity.
A mathematical model relating neural activity to cerebral blood flow. An ageing population is increasingly prone to neurodegenerative disease and the associated mental impairment can severely disrupt the lives of both the sufferers and the carers. Non-invasive brain imaging techniques are used to both diagnose and supervise treatment of such disease, but at present a lack of understanding of the underlying physiology leaves these methods open to criticism. The construction of a detailed quanti ....A mathematical model relating neural activity to cerebral blood flow. An ageing population is increasingly prone to neurodegenerative disease and the associated mental impairment can severely disrupt the lives of both the sufferers and the carers. Non-invasive brain imaging techniques are used to both diagnose and supervise treatment of such disease, but at present a lack of understanding of the underlying physiology leaves these methods open to criticism. The construction of a detailed quantitative model of the basic processes underlying this imaging will enable precise interpretation of such brain scans and increase their usefulness both as a research and as a therapeutic tool.Read moreRead less
A novel role for microglia in neural maturation. This project aims to determine the role that microglia have in maturation of cells of the retina called photoreceptors. High resolution microscopy combined with molecular and functional analysis will show the extent and type of contact between photoreceptors and microglia, the molecules released by microglia and the mechanism(s) by which microglia modify photoreceptors after birth. The knowledge gained in this project will provide critical informa ....A novel role for microglia in neural maturation. This project aims to determine the role that microglia have in maturation of cells of the retina called photoreceptors. High resolution microscopy combined with molecular and functional analysis will show the extent and type of contact between photoreceptors and microglia, the molecules released by microglia and the mechanism(s) by which microglia modify photoreceptors after birth. The knowledge gained in this project will provide critical information about how we see, and will have sustained impact on our understanding of the role of immune cells in the nervous system.Read moreRead less
Deconstructing the neural circuits regulating appetite. This project aims to expand our knowledge about the neural circuits that influence a feeding response in the absence of emotional or cognitive obstacles. Feeding behaviour is a fundamental physiological process in all animals. Despite the seemingly simple endpoint, feeding behaviour is affected by numerous factors including stress and motivation that can inhibit feeding behaviour. This knowledge is critical to maximise growth and survival i ....Deconstructing the neural circuits regulating appetite. This project aims to expand our knowledge about the neural circuits that influence a feeding response in the absence of emotional or cognitive obstacles. Feeding behaviour is a fundamental physiological process in all animals. Despite the seemingly simple endpoint, feeding behaviour is affected by numerous factors including stress and motivation that can inhibit feeding behaviour. This knowledge is critical to maximise growth and survival in many Australian sectors including agriculture, conservation and basic science.Read moreRead less
Early life overfeeding - mechanisms for programming obesity and long-term immune dysfunction. Early life overfeeding can lead to obesity and related changes in adulthood. With this study we will discover how overfeeding can permanently alter an animal's development so that its body weight and immune functions are dysregulated. The outcomes will facilitate appropriate design of animal experiments considering the impact of neonatal programming. They will also contribute to more efficient feeding p ....Early life overfeeding - mechanisms for programming obesity and long-term immune dysfunction. Early life overfeeding can lead to obesity and related changes in adulthood. With this study we will discover how overfeeding can permanently alter an animal's development so that its body weight and immune functions are dysregulated. The outcomes will facilitate appropriate design of animal experiments considering the impact of neonatal programming. They will also contribute to more efficient feeding protocols for meat production in agriculture and identify targets for risk management and for preventing and ameliorating early life overfeeding effects in humans. This investigation therefore has clear benefits to the social, economic, and health aspects of obesity and to basic science and agriculture.Read moreRead less
Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechan ....Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechanisms by which these compounds act. By discovering their site and mechanisms of action we will further our understanding of these important proteins and their modulation, maintain Australia's significant expertise in this field and provide leads for future development of drugs with potential therapeutic value.Read moreRead less
Understanding how the brain uses sensory information to guide reaching and grasping movements. Reaching, grasping and manipulating objects are crucial aspects of our daily lives, which are performed so effortlessly that they tend to be taken for granted. We know however that these functions take a relatively long time to mature (think of a baby learning how to get an object), and that they can be impaired by brain lesions involving a region called the posterior parietal cortex. We also know that ....Understanding how the brain uses sensory information to guide reaching and grasping movements. Reaching, grasping and manipulating objects are crucial aspects of our daily lives, which are performed so effortlessly that they tend to be taken for granted. We know however that these functions take a relatively long time to mature (think of a baby learning how to get an object), and that they can be impaired by brain lesions involving a region called the posterior parietal cortex. We also know that this region has multiple subdivisions, but how exactly these interact in allowing the sensory information to guide arm and hand muscles is unknown. Discovering how this happens in terms of cellular interaction can have profound implications for the creation of new technologies such as artificial limbs and autonomous robots, and result in health benefits.Read moreRead less