Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests tha ....Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests that changes in presenilin function in aged cells might be a common molecular link between spontaneous and inherited Alzheimer's disease and could contribute to frontotemporal dementia and cancer. Our research will show whether this phenomenon might provide a breakthrough in our understanding of these diseases and be a productive area for research into their amelioration and/or prevention.Read moreRead less
Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods ....Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods to simplify the analysis of multimodal path-clamping data (Patch-seq). Expected outcomes will facilitate research collaboration and the reproducibility of accurate experimental replicates of the human brain. This will provide significant benefits in the global race to understand human brain computation mechanisms.Read moreRead less
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
The prediction of sleep/wake behaviour based on physiological and social factors. The prevalence of shiftwork has increased in Australia over the last few decades. Shiftworkers obtain less sleep, have greater difficulty maintaining good relationships, have poorer health, and are more likely to be injured at work than others. Using the largest dataset of its kind, we will substantially contribute to understanding the relationships between work hours, sleep, performance and safety. Ultimately, the ....The prediction of sleep/wake behaviour based on physiological and social factors. The prevalence of shiftwork has increased in Australia over the last few decades. Shiftworkers obtain less sleep, have greater difficulty maintaining good relationships, have poorer health, and are more likely to be injured at work than others. Using the largest dataset of its kind, we will substantially contribute to understanding the relationships between work hours, sleep, performance and safety. Ultimately, the project will answer a question critical to workplace safety - how much time off between shifts is needed to be alert and safe at work? The project will also produce tools to help industry design fatigue-friendly rosters, improving the safety, productivity and general well-being of shiftworkers in Australia and overseas.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453073
Funder
Australian Research Council
Funding Amount
$129,485.00
Summary
Establishment of a South Australian rTMS Facility. It is proposed to establish a South Australian Facility for rapid rate transcranial magnetic stimulation (TMS) which will be the only one in Australia. This Facility will provide enormous opportunities for collaborative cutting edge investigations into the role of the human cortical areas in a diverse range of tasks. For example, projects have been identified projects employing rTMS to study sensorimotor cortical plasticity, facilitate functiona ....Establishment of a South Australian rTMS Facility. It is proposed to establish a South Australian Facility for rapid rate transcranial magnetic stimulation (TMS) which will be the only one in Australia. This Facility will provide enormous opportunities for collaborative cutting edge investigations into the role of the human cortical areas in a diverse range of tasks. For example, projects have been identified projects employing rTMS to study sensorimotor cortical plasticity, facilitate functional recovery following stroke and investigate the mechanisms of savant behaviour. Provision of this Facility will provide further support for this productive and internationally renowned group of scientists to develop their research programs.Read moreRead less
Uncovering the processes underlying human category learning. There is a pervasive belief that complex tasks can somehow be learned via a 'smart' implicit or procedural learning mechanism, which operates independently of memory and attention. This idea has important implications for our understanding of cognition. If true, there seems little point in providing explicit instruction in such tasks, and efforts to do so are, at best, wasted time and, at worst, detrimental to the learning process. Th ....Uncovering the processes underlying human category learning. There is a pervasive belief that complex tasks can somehow be learned via a 'smart' implicit or procedural learning mechanism, which operates independently of memory and attention. This idea has important implications for our understanding of cognition. If true, there seems little point in providing explicit instruction in such tasks, and efforts to do so are, at best, wasted time and, at worst, detrimental to the learning process. This project will provide much-needed scrutiny of this idea and will help not only to re-orient our understanding of how we deal with complex information, but will also highlight issues about data interpretation that are fundamental for the research and wider communities.Read moreRead less
Understanding the molecular mechanisms of intellectual disability. Intellectual disability is frequent in the population, with one in every fifty people in the world directly affected. This project will improve our understanding of the correct development and function of the brain required for cognition by investigating specific roles and regulation of key molecules involved.
The effect of temperature biofeedback on sleep and cardiac autonomic tone in young and aged adults. Peripheral heat loss is reported to promote sleep onset. To date, however, most studies examining the thermoregulatory model of sleep onset have used sedative-hypnotics with both thermoregulatory and soporific effects. We propose that a better test of a causal relationship between peripheral heat loss and sleep can be achieved by using temperature biofeedback; a promising non-invasive and non-dr ....The effect of temperature biofeedback on sleep and cardiac autonomic tone in young and aged adults. Peripheral heat loss is reported to promote sleep onset. To date, however, most studies examining the thermoregulatory model of sleep onset have used sedative-hypnotics with both thermoregulatory and soporific effects. We propose that a better test of a causal relationship between peripheral heat loss and sleep can be achieved by using temperature biofeedback; a promising non-invasive and non-drug treatment that does not have a direct effect on sleep structures. We aim to test whether increased peripheral heat loss promotes sleep onset, whether the effects are mediated by changes in autonomic tone, and whether this relationship changes with age.Read moreRead less
Behavioural syndromes and social networks in sleepy lizards. Fauna in Australian ecosystems are threatened by habitat fragmentation, changing environments and the spread of exotic pathogens. To manage these threats we need to understand the behavioural flexibility of wildlife populations. This project focuses on how individual behavioural differences can influence social networks and consequently pathogen transmission. It will help to protect our fauna from invasive diseases and contribute to su ....Behavioural syndromes and social networks in sleepy lizards. Fauna in Australian ecosystems are threatened by habitat fragmentation, changing environments and the spread of exotic pathogens. To manage these threats we need to understand the behavioural flexibility of wildlife populations. This project focuses on how individual behavioural differences can influence social networks and consequently pathogen transmission. It will help to protect our fauna from invasive diseases and contribute to sustaining biodiversity. With better knowledge of how diseases spread we can develop more effective controls of those diseases, thereby protecting wildlife species, animal populations and Australian ecosystems. Read moreRead less