Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
Processing of social communication calls in primate auditory cortex. This research will advance our understanding of the brain mechanisms involved in perception of sound. This will help to understand disorders of speech and hearing following brain damage and may assist in efforts to develop better hearing aids, as well as other speech recognition technologies. In addition, we will develop a primate for studying processing of sound in the brain that will be useful in future research to develop ....Processing of social communication calls in primate auditory cortex. This research will advance our understanding of the brain mechanisms involved in perception of sound. This will help to understand disorders of speech and hearing following brain damage and may assist in efforts to develop better hearing aids, as well as other speech recognition technologies. In addition, we will develop a primate for studying processing of sound in the brain that will be useful in future research to develop improved cochlear implants.Read moreRead less
The long-term consequences of toluene exposure on the maturing brain. Inhalant abuse is a significant problem especially among adolescent and indigenous communities. This project will provide insights into the long-term neurobiological consequences following inhalant exposure during adolescence when critical aspects of brain development are still occurring and how these may relate to altered behaviour in adulthood.
Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understandin ....Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understanding of one brain region that is known to contribute to the development of cardiovascular disease. It is expected that increased knowledge of brain function will lead to novel theories of brain disease and therapeutic strategies.Read moreRead less
Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will im ....Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will improve our mechanistic understanding of genetic diseases in populations. In addition, this proposal is expected to lead to identification of potential targets and technologies that would be of interest to Australian industry.Read moreRead less
Neural circuit control of effort under stress . This Project aims to investigate how the ‘decision’ to persist in exerting effort to obtain a reward is encoded in the the brain and affected by stress. This work will generate new knowledge on the neural mechanisms through which stress modifies neural activity to control decision making processes underpinning adaptive behaviours essential for survival. The expected outcomes of this work include enhanced capacity at the interface of behavioural a ....Neural circuit control of effort under stress . This Project aims to investigate how the ‘decision’ to persist in exerting effort to obtain a reward is encoded in the the brain and affected by stress. This work will generate new knowledge on the neural mechanisms through which stress modifies neural activity to control decision making processes underpinning adaptive behaviours essential for survival. The expected outcomes of this work include enhanced capacity at the interface of behavioural and computational neuroscience, that will in turn provide significant benefits through greater insight into brain functions essential for survival, with long ranging implications for performance optimisation and brain-inspired computing. Read moreRead less
Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. 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 ....Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. 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
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
Temporal interactions of dorsal/ventral visual streams. This project aims to understand the temporal interactions between the dorsal and ventral visual streams that control skilled actions. The neural pathways for visual perception of objects may be distinct from those associated with movements towards the object, but the speed of activation and interactions of these two cortical visual streams have not been investigated. This project will use the temporal sensitivity of neuroscience brain imagi ....Temporal interactions of dorsal/ventral visual streams. This project aims to understand the temporal interactions between the dorsal and ventral visual streams that control skilled actions. The neural pathways for visual perception of objects may be distinct from those associated with movements towards the object, but the speed of activation and interactions of these two cortical visual streams have not been investigated. This project will use the temporal sensitivity of neuroscience brain imaging techniques (MEG, EEG, fMRI) to measure the real-time sequence of interactions between the two visual streams during goal-directed grasping. It intends to extend the most influential model of visual processing by discovering ‘when’ these pathways activate and interact. Such knowledge will affect delivery of social and commercial outcomes, by providing new directions for the rehabilitation of sensorimotor performance in many neurodevelopmental disorders, and by improving design of control systems for robotic effectors, prosthetic limbs, and more seamless human-machine interfaces.Read moreRead less