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
Role of the complement system in the healthy and diseased central nervous system. The investigation into the role of the immune system in the central nervous system will increase our understanding of the causes behind the neurodegenerative process in aging individuals. This research will also indicate the potential for new types of anti-inflammatory drugs, to be used to slow the neurodegenerative process occurring naturally in the aging brain. These drugs could also be useful in treating drastic ....Role of the complement system in the healthy and diseased central nervous system. The investigation into the role of the immune system in the central nervous system will increase our understanding of the causes behind the neurodegenerative process in aging individuals. This research will also indicate the potential for new types of anti-inflammatory drugs, to be used to slow the neurodegenerative process occurring naturally in the aging brain. These drugs could also be useful in treating drastic neurodegenerative diseases such as motor neuron disease, Huntington's disease and Parkinson's disease. Of these, only Parkinson's disease currently has some effective treatments. Community and National benefits would be increased health, decreased stress and major economic savings.Read moreRead less
The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciph ....The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciphering basic biological mechanisms, patenting new data, developing treatment strategies for un-curable and fatal disorders, and expanding links to Australian biotech and international pharmaceutical companies.Read moreRead less
Novel role of RNA methylation in neuronal homeostasis. This proposal is aimed at understanding the RNA signalling that takes place in neuronal homeostatic response. The crucial role of neuronal homeostasis for normal brain function is evidenced throughout the nervous system; however, the precise underlying mechanisms are still not well understood. The proposed research will utilise high-throughput sequencing approaches coupled with biochemical, molecular and cell biological assays to provide mec ....Novel role of RNA methylation in neuronal homeostasis. This proposal is aimed at understanding the RNA signalling that takes place in neuronal homeostatic response. The crucial role of neuronal homeostasis for normal brain function is evidenced throughout the nervous system; however, the precise underlying mechanisms are still not well understood. The proposed research will utilise high-throughput sequencing approaches coupled with biochemical, molecular and cell biological assays to provide mechanistic insights into the molecular processes that control neuronal homeostatic responses. This will elucidate how neural plasticity and network stability are maintained, a process that is critical for our understanding of sensory processing, learning and memory throughout life.Read moreRead less
How brains become lateralised. This project aims to understand how the left and right sides of the brain become specialised for different cognitive functions, a phenomenon called lateralisation. Lateralisation is one of the least understood organisational principles of the brain, yet is crucial to the way we think and behave. Manifested most clearly as handedness, the brain is lateralised for many cognitive tasks such as language, reasoning, memory and emotion. However, the developmental origin ....How brains become lateralised. This project aims to understand how the left and right sides of the brain become specialised for different cognitive functions, a phenomenon called lateralisation. Lateralisation is one of the least understood organisational principles of the brain, yet is crucial to the way we think and behave. Manifested most clearly as handedness, the brain is lateralised for many cognitive tasks such as language, reasoning, memory and emotion. However, the developmental origin and anatomical substrate of most cognitive asymmetries are unknown. This project will use a chick model of brain lateralisation to quantify and localise to specific brain circuits the patterns of differential gene expression that give rise to anatomical and functional asymmetries.Read moreRead less
Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and w ....Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and whether neurogenesis may be induced by inflammation in the adult. Using transcriptomics we will also determine how the neurogenic environment changes with age/inflammation. This project is an important step in proving that the brain's potential to generate new neurons extends beyond infancy.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
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
The role of RNA editing by the brain-specific enzym ADAR3 in learning and memory. Higher-order cognition sets us apart from other species but how this is achieved is still under debate. The project will test the idea, strongly supported by recent genomic analyses, that subtle changes in the sequences of RNA in response to environmental stimuli underpin this extraordinary ability.
Investigating differences in decision-making ability in older adults. This project aims to investigate how healthy ageing impacts decision making and its associated neural circuits using computation modelling and neurogenetic methods. Decision-making is a fundamental cognitive ability, allowing us to choose the best course of action. This project will investigate the relationship between genes and decision-making performance across the adult lifespan. Expected outcomes include a deeper understan ....Investigating differences in decision-making ability in older adults. This project aims to investigate how healthy ageing impacts decision making and its associated neural circuits using computation modelling and neurogenetic methods. Decision-making is a fundamental cognitive ability, allowing us to choose the best course of action. This project will investigate the relationship between genes and decision-making performance across the adult lifespan. Expected outcomes include a deeper understanding of how decision-making evolves in healthy ageing, and a tool based on genetic scores and computational modelling to predict an individual's trajectory of cognitive function. This could help identify individuals who are at risk for cognitive decline, which could then inform better interventions.Read moreRead less