Vulnerability to cocaine use: discovering common mechanisms conserved across animal phyla. Drug abuse costs Australia an estimated $ 20 billion each year, and research is urgently needed to understand how drugs cause long-term behavioural dysfunction. Our research will identify the basal cellular mechanisms underlying drug abuse and addiction, which are likely to be the best targets for therapies to prevent and cure addiction. Our findings are also relevant to other neuropsychiatric disorders r ....Vulnerability to cocaine use: discovering common mechanisms conserved across animal phyla. Drug abuse costs Australia an estimated $ 20 billion each year, and research is urgently needed to understand how drugs cause long-term behavioural dysfunction. Our research will identify the basal cellular mechanisms underlying drug abuse and addiction, which are likely to be the best targets for therapies to prevent and cure addiction. Our findings are also relevant to other neuropsychiatric disorders related to drug abuse (e.g. depression, anxiety) that are on the increase in Australia. Our work will enhance Australia's reputation for neuroscience research, and will provide training for students in neuropharmacology and molecular neurobiology.Read moreRead less
Neurological cell replacement therapies: improving outcomes by matching developmental profiles of transplanted cells with the damaged brain area. Stem cell transplantation offers a way to replace nerve cells lost due to acute CNS injury or chronic degenerative conditions such as Parkinson's Disease. However, to date, results have been disappointing because of poor differentiation, survival and integration of stem cells confounded by ethical issues associated with the use of embryos as the source ....Neurological cell replacement therapies: improving outcomes by matching developmental profiles of transplanted cells with the damaged brain area. Stem cell transplantation offers a way to replace nerve cells lost due to acute CNS injury or chronic degenerative conditions such as Parkinson's Disease. However, to date, results have been disappointing because of poor differentiation, survival and integration of stem cells confounded by ethical issues associated with the use of embryos as the source of stem cells. The experiments conducted in this study will provide strategies to improve the efficacy of stem cell transplantation into the damaged CNS as well as developing the use of autologous bone marrow stem cells for repair. Outcomes will be improved transplant methodologies and expertise for the bio-technology industry. Read moreRead less
Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application i ....Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application in medicine and the drug industry. This research is highly significant in relation to human health. The biological and nutritional aspects of polyunsaturated lipids and dietary fish oils have long been recognized. Thus this project will provide further knowledge that could benefit the health of the nation with consequent reduced health care costs.Read moreRead less
Investigating the Molecular Mechanism of Synaptic Transmission. This project aims to increase our understanding of the synaptic function of the nervous system. Neurons communicate with each other via the release of neurotransmitters at specialised structures known as synapses. Synaptic vesicle (SV) release from the presynaptic neuron is essential for this neuronal transmission, which drives all aspects of nervous system function, including behaviour and cognition. This project plans to investiga ....Investigating the Molecular Mechanism of Synaptic Transmission. This project aims to increase our understanding of the synaptic function of the nervous system. Neurons communicate with each other via the release of neurotransmitters at specialised structures known as synapses. Synaptic vesicle (SV) release from the presynaptic neuron is essential for this neuronal transmission, which drives all aspects of nervous system function, including behaviour and cognition. This project plans to investigate how key synaptic proteins and the interactions between them regulate spontaneous SV release. It aims to reveal the molecular mechanism of both basal level regulation and the potentiation of spontaneous SV release, using a Caenorhabditis elegans model system.Read moreRead less
Insulin transport into the central nervous system. This project aims to understand transportation of peripheral insulin into the central nervous system and how it maintains energy balance. Insulin is essential for normal physiological functioning in the periphery and central nervous system, but some circumstances, including high-fat diets, reduce insulin signalling in the brain. This project examines the mechanisms of insulin transport into the central nervous system, and may improve our underst ....Insulin transport into the central nervous system. This project aims to understand transportation of peripheral insulin into the central nervous system and how it maintains energy balance. Insulin is essential for normal physiological functioning in the periphery and central nervous system, but some circumstances, including high-fat diets, reduce insulin signalling in the brain. This project examines the mechanisms of insulin transport into the central nervous system, and may improve our understanding of blood brain barrier insulin transport and dysfunction.Read moreRead less
Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting ....Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting them in mice, testing for developmental, cognitive and motor effects, and characterising the structures with which they are associated. The results of the project are expected to open new vistas in neuroscience, contributing to understanding the molecular basis of brain function and the 'dark matter' of the genome.Read moreRead less
Molecular dissection of the effects of alpha-actinin-3 deficiency on normal variation in skeletal muscle function. We will study the mechanisms by which a common genetic variant influences muscle bulk, muscle strength and the metabolic efficiency of muscle in the general population. Common genetic variants that influence skeletal muscle function have major potential public health implications as they are likely to influence individuals' response to exercise and diet, and to contribute to suscept ....Molecular dissection of the effects of alpha-actinin-3 deficiency on normal variation in skeletal muscle function. We will study the mechanisms by which a common genetic variant influences muscle bulk, muscle strength and the metabolic efficiency of muscle in the general population. Common genetic variants that influence skeletal muscle function have major potential public health implications as they are likely to influence individuals' response to exercise and diet, and to contribute to susceptibility to common diseases such as obesity, diabetes, and the loss of muscle strength in the elderly. In addition, the identification of genetic factors that influence muscle bulk in vertebrates has implications for breeding programs in sheep and cattle and may provide commercial benefit to the livestock industry.Read moreRead less
How do interactions between axon guidance molecules bring about directed axon growth? This project deals with a fundamental, yet poorly understood biological problem at the cutting edge of international science - how axons navigate to their targets. A better understanding of this basic biological process will greatly assist the development of therapies to treat a wide range of clinical conditions in which axonal connections between neurons are disrupted by trauma or disease.
Specialized glial cells within the hippocampus of the brain regulate important morphological events in embryonic development. Memories of past experiences, and our ability to learn new information, is processed in a region of the brain called the hippocampus. In order for this to occur, the cells that make up the hippocampus must form correctly during embryonic development. This proposal investigates the cellular and molecular mechanisms regulating hippocampal formation. The national benefit of ....Specialized glial cells within the hippocampus of the brain regulate important morphological events in embryonic development. Memories of past experiences, and our ability to learn new information, is processed in a region of the brain called the hippocampus. In order for this to occur, the cells that make up the hippocampus must form correctly during embryonic development. This proposal investigates the cellular and molecular mechanisms regulating hippocampal formation. The national benefit of this work is to provide basic knowledge about the processes that underlie correct brain formation and function, and to understand what processes are disrupted when the brain fails to function correctly. Such disruptions lead to mental retardation and learning difficulties, and in the aged, an inability to form and store new memories, as occurs in dementia.Read moreRead less
Are neurobehavioural and neuromotor impairments associated with FMR1 gene expansion? The gene that causes Fragile X syndrome is found at the end of the X chromosome and is present in all humans. In many cases there is a small to medium change in this gene that may cause psychological and motor difficulties in later adulthood. The core aim of this project is to identify early age-related changes that would indicate later neurological decline.