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.
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
Coding of olfactory information in the piriform cortex. This project aims to understand how electrical activity in the primary olfactory (piriform) cortex enables mice to recognise and remember odours. By using optical recording techniques together with genetic tools, the project expects to generate new knowledge about how the mammalian brain builds internal representations of the external world. Specific outcomes of the project include new insights into the functional architecture of the pirifo ....Coding of olfactory information in the piriform cortex. This project aims to understand how electrical activity in the primary olfactory (piriform) cortex enables mice to recognise and remember odours. By using optical recording techniques together with genetic tools, the project expects to generate new knowledge about how the mammalian brain builds internal representations of the external world. Specific outcomes of the project include new insights into the functional architecture of the piriform cortex and fresh understanding of how olfactory information is encoded and stored in neural circuits. More broadly, the project aims to advance our understanding of how the brain works, with benefits for future improvements in artificial intelligence and brain-machine interfaces.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
Using nanostructured biomaterials and stem cells to repair spinal cord injuries. There is currently no effective cure for spinal cord injuries and the consequences to the patient are devastating. Spinal cord injuries affects limb, bowel, bladder and sexual function, and many people with these injuries strugle to maintain their independence. Because people can live for many years after spinal cord damage, the financial and social costs are immense, as many are dependent on the help of others for ....Using nanostructured biomaterials and stem cells to repair spinal cord injuries. There is currently no effective cure for spinal cord injuries and the consequences to the patient are devastating. Spinal cord injuries affects limb, bowel, bladder and sexual function, and many people with these injuries strugle to maintain their independence. Because people can live for many years after spinal cord damage, the financial and social costs are immense, as many are dependent on the help of others for their survival. This proposal tackles this urgent problem by applying advanced nanostructured materials with stem cells, to assist the body in the repair of the spinal cord following injury. Read moreRead less
Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will c ....Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will construct a set of physical models of biological ion channels, which will correctly replicate experimental observations. Such a theory will link the structure and function of an ion channel through the fundamental principles of physics.Read moreRead less