Improving neuronal cell function with cell permeable copper complexes. Metal-based drugs offer an exciting new approach to treatment of neurodegeneration. However, little is known about how cells metabolise these drugs and this information is critical for further drug development. This project will determine how metal-based drugs are metabolised by neuronal cells and how this may result in therapeutic benefit.
Resolving the Structures of Human Muscarinic M1 and M4 Receptors. Muscarinic receptors are vital for most basic human brain functions. These receptors are changed in schizophrenia and Alzheimer's disease. This project will determine the structure and localisation of two of these receptors in order to i) understand their roles in brain disorders and ii) develop drugs to treat disorders involving them.
The basis of conscious thought. The science and philosophy of consciousness has made much progress in recent years, and the study of conscious thought is the next frontier. The project will place Australian research on the leading edge of this area. An international network of researchers will analyse both the neurobiological basis and the subjective experience of conscious thought, yielding a unified account of conscious thinking from the first-person and third-person perspectives. The resultin ....The basis of conscious thought. The science and philosophy of consciousness has made much progress in recent years, and the study of conscious thought is the next frontier. The project will place Australian research on the leading edge of this area. An international network of researchers will analyse both the neurobiological basis and the subjective experience of conscious thought, yielding a unified account of conscious thinking from the first-person and third-person perspectives. The resulting account will illuminate the nature of human thinking and reasoning, and will be applied to the detection of consciousness in post-coma patients.Read moreRead less
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Engineering functional nerves using microtailored culture systems. The aim of this work is to develop new culture systems for developing and growing nerves outside of the body. The project will generate knowledge and engineering technology for production of neural implants suitable for medical applications. The availability of engineered nerve grafts to repair neural injuries will improve patient health outcomes.
Peripheral and central mechanisms of sensory coding and integration. The research described in this proposal seeks to provide generic answers to fundamental questions about sensory processes, the nature of perceptual experience, and how these are subserved by the nervous system. The study of inter-sensory interactions in perception has the potential to be incorporated into the development of virtual reality-type computer-based technologies. The neurophysiology research will provide basic informa ....Peripheral and central mechanisms of sensory coding and integration. The research described in this proposal seeks to provide generic answers to fundamental questions about sensory processes, the nature of perceptual experience, and how these are subserved by the nervous system. The study of inter-sensory interactions in perception has the potential to be incorporated into the development of virtual reality-type computer-based technologies. The neurophysiology research will provide basic information that has the potential to deepen our understanding, and even enhance possible treatment, of neurological conditions that involve sensory systems.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
How do myelinating cells alter brain circuits to facilitate learning? This project aims to identify the brain circuits that receive new insulation and characterise the molecular mediators of this process. This project will apply innovative technologies to understand how the nervous system remains adaptable throughout life. This new knowledge, of the cellular mechanisms that allow brain circuits to remain adaptable throughout life, may have application in the development of interventions aimed at ....How do myelinating cells alter brain circuits to facilitate learning? This project aims to identify the brain circuits that receive new insulation and characterise the molecular mediators of this process. This project will apply innovative technologies to understand how the nervous system remains adaptable throughout life. This new knowledge, of the cellular mechanisms that allow brain circuits to remain adaptable throughout life, may have application in the development of interventions aimed at improving educational outcomes or counteracting age-related memory decline. Potential future benefits include facilitating the development of drugs to circumvent memory loss resulting from brain diseases, and improving the design of neuromorphic hardware for computing.Read moreRead less
Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales ....Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales with molecular dynamics at small distances and shorter times. Applications to both membrane proteins (blocking of ion channels by toxins and drugs) and globular proteins (ligand binding to receptors and protein association) will be considered.Read moreRead less
What is normal brain ageing? An investigation of changes in brain structure and cognition in mid-life. Pathological brain changes associated with cognitive decline later in life become detectable in the 40s and sometimes earlier, yet little is known about what constitute normal brain ageing in midlife. Using a number of neuroimaging techniques, this project will develop a detailed map of brain and cognitive ageing in middle-age and their predictors.