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 mathematical model of calcium signalling in single cells and in multicellular systems. Calcium released from stores inside cells plays a vital signalling role in living organisms. It initiates cell division after fertilization, mediates communication and learning in the nervous system, causes contraction in the muscular walls of arteries and plays an important but as yet poorly understood role in the information processing that occurs in systems of coupled glial cells. We will construct a uni ....A mathematical model of calcium signalling in single cells and in multicellular systems. Calcium released from stores inside cells plays a vital signalling role in living organisms. It initiates cell division after fertilization, mediates communication and learning in the nervous system, causes contraction in the muscular walls of arteries and plays an important but as yet poorly understood role in the information processing that occurs in systems of coupled glial cells. We will construct a unified mathematical model of calcium signalling in multicellular systems, starting from the known processes in single cells, and use it to gain insight into the functioning and possible dysfunctioning of calcium-mediated intercellular communication.Read moreRead less
The implications of resistance training for the control of movement. Resistance training (or weight lifting) is an essential element of comprehensive rehabilitation programs in a wide range of clinical settings. However, because we know little about how the organization of the nervous system is affected by training with high loads, the consequences of resistance training for our ability to control functional movements are unclear. The ultimate goal of this research is to generate basic knowledge ....The implications of resistance training for the control of movement. Resistance training (or weight lifting) is an essential element of comprehensive rehabilitation programs in a wide range of clinical settings. However, because we know little about how the organization of the nervous system is affected by training with high loads, the consequences of resistance training for our ability to control functional movements are unclear. The ultimate goal of this research is to generate basic knowledge about the impact of resistance training on nervous system function. The research will lead to the design of injury prevention and rehabilitation programs that are maximally effective, and provide a genuine benefit to the community.Read moreRead less
Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a gr ....Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Development of integrated biological markers of brain function. With the rapid growth of both brain imaging and genetics, we can now examine the biological basis of complex brain functions, such as memory. Our goal is to combine these techniques to develop evidence-based biological markers of normal function. These markers can then be used to screen for early signs of abnormal function (eg. in Alzheimer's disease) and to assess treatment effects. Two unique features ensure the project's feasibil ....Development of integrated biological markers of brain function. With the rapid growth of both brain imaging and genetics, we can now examine the biological basis of complex brain functions, such as memory. Our goal is to combine these techniques to develop evidence-based biological markers of normal function. These markers can then be used to screen for early signs of abnormal function (eg. in Alzheimer's disease) and to assess treatment effects. Two unique features ensure the project's feasibility: a) access to the first standardized, normative brain database (from the Brain Resource Company Ltd) and b) a scientific collaboration supporting the integration of brain imaging and genetics.Read moreRead less
Regulation of Stress Hormone Receptors in the Brain. Our research will provide information on how the brain controls our response to stress and will allow the development of targeted strategies to reduce the possibility during chronic stress of the development of conditions such as anxiety and depression. This will improve mental health outcomes in Australia and add to Australia's economic and social stability.
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
Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operati ....Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operation and seeking cures for diseases caused by their malfunction. This project aims to develop accurate ion-protein-water interactions for permeation models based on stochastic and molecular dynamics simulations using both classical and quantum mechanical methods.Read moreRead less
Quantum mechanical and dynamical investigation of ion channels. Many genetic diseases result from mutations in the genes that transcribe the channel proteins. Ion channels are also primary targets for development of therapeutic drugs for many ailments. Development of proper simulation tools is essential for a molecular-level understanding of their operation, which will be very helpful in finding treatments for genetic diseases as well as new drugs that target ion channels. Another aim of the p ....Quantum mechanical and dynamical investigation of ion channels. Many genetic diseases result from mutations in the genes that transcribe the channel proteins. Ion channels are also primary targets for development of therapeutic drugs for many ailments. Development of proper simulation tools is essential for a molecular-level understanding of their operation, which will be very helpful in finding treatments for genetic diseases as well as new drugs that target ion channels. Another aim of the project is to provide research training in computational biology. Research in this area is rapidly growing elsewhere but it has been rather neglected in Australia, and there is a shortage of researchers with such skills at present.Read moreRead less
Validation of a New Conceptual Model of ADHD based on Underlying Central Nervous System Dysfunction. ADHD is a debilitating problem that affects 5% of children and approximately half as many adults. ADHD causes substantial problems at school and if untreated, predisposes the individual to increased drug and alcohol use, marital breakdown, criminal prosecution and psychiatric problems in later life. One problem is that we do not fully understand what are the causes of the disorder. This project w ....Validation of a New Conceptual Model of ADHD based on Underlying Central Nervous System Dysfunction. ADHD is a debilitating problem that affects 5% of children and approximately half as many adults. ADHD causes substantial problems at school and if untreated, predisposes the individual to increased drug and alcohol use, marital breakdown, criminal prosecution and psychiatric problems in later life. One problem is that we do not fully understand what are the causes of the disorder. This project will test the validity of several models of brain dysfunction in ADHD which have been influential in the literature, but poorly tested. Through better understanding of the basic underlying problems, more effective intervention can be developed.Read moreRead less