INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generat ....INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generate synchronised neuronal activity. This project aims to investigate mechanisms underlying a specific class of brain rhythm implicated in control of mood states. Positive outcomes from this basic research may lead to better drug therapies for controlling specific mental disorders.Read moreRead less
Physiology of tau protein: a novel role in scaffolding and intracellular distribution. Understanding brain function remains a challenge. This project will study the normal role of the Alzheimer's disease-related protein tau in brain function during ageing. This will significantly enhance current understanding of brain function.
Towards direct imaging of neuronal currents with MRI. This project aims to develop novel neuronal current magnetic resonance imaging (nc-MRI) methods that harness the oscillatory behaviour of neuronal magnetic fields. Current methods of detecting neuronal activity in the living human brain have limited spatial and temporal resolution. Use of nc-MRI aims to overcome these limitations by imaging the effects on the MRI signal of small transient magnetic fields associated with neuronal activity. Sig ....Towards direct imaging of neuronal currents with MRI. This project aims to develop novel neuronal current magnetic resonance imaging (nc-MRI) methods that harness the oscillatory behaviour of neuronal magnetic fields. Current methods of detecting neuronal activity in the living human brain have limited spatial and temporal resolution. Use of nc-MRI aims to overcome these limitations by imaging the effects on the MRI signal of small transient magnetic fields associated with neuronal activity. Signal-to-noise ratio is at the limits of detectability using current imaging systems and nc-MRI is yet to be convincingly demonstrated. An integrated framework for simulating nc-MRI in the visual cortex is expected to be developed.Read moreRead less
Control of cellular differentiation in the developing brain. This project aims to understand how mature brain cells form during foetal life. The central hypothesis is that a specific transcription factor family, called NFI, regulates the epigenetic state of the cell, allowing chromatin accessibility and subsequent transcriptional activation and repression to control cellular differentiation. Aims 1 and 2 will investigate how brain cells transition from proliferating progenitor cells to different ....Control of cellular differentiation in the developing brain. This project aims to understand how mature brain cells form during foetal life. The central hypothesis is that a specific transcription factor family, called NFI, regulates the epigenetic state of the cell, allowing chromatin accessibility and subsequent transcriptional activation and repression to control cellular differentiation. Aims 1 and 2 will investigate how brain cells transition from proliferating progenitor cells to differentiated mature cell types. Aim 3 will investigate how differentiation is maintained in the adult brain. Methods used involve genome and chromatin analyses of cells isolated from transgenic mouse models. Outcomes and benefits are substantial knowledge gain applicable to stem cell regulation and brain health.Read moreRead less
Neurological cell replacement therapies: improving outcomes by matching developmental profiles of transplanted cells with the damaged brain area. Stem cell transplantation offers a way to replace nerve cells lost due to acute CNS injury or chronic degenerative conditions such as Parkinson's Disease. However, to date, results have been disappointing because of poor differentiation, survival and integration of stem cells confounded by ethical issues associated with the use of embryos as the source ....Neurological cell replacement therapies: improving outcomes by matching developmental profiles of transplanted cells with the damaged brain area. Stem cell transplantation offers a way to replace nerve cells lost due to acute CNS injury or chronic degenerative conditions such as Parkinson's Disease. However, to date, results have been disappointing because of poor differentiation, survival and integration of stem cells confounded by ethical issues associated with the use of embryos as the source of stem cells. The experiments conducted in this study will provide strategies to improve the efficacy of stem cell transplantation into the damaged CNS as well as developing the use of autologous bone marrow stem cells for repair. Outcomes will be improved transplant methodologies and expertise for the bio-technology industry. Read moreRead less
Phenotyping doublecortin+ cells to unravel human adult neurogenesis. This project investigates one of the brain’s most remarkable phenomena: adult neurogenesis, the birth of new brain cells in a specialised brain area (the hippocampus) occurring well into adulthood. This process contributes to many species’ capacity to learn, remember and regenerate. However whether this process occurs in humans is heavily debated. Using new neuroscience tools, this project will produce new insights into human a ....Phenotyping doublecortin+ cells to unravel human adult neurogenesis. This project investigates one of the brain’s most remarkable phenomena: adult neurogenesis, the birth of new brain cells in a specialised brain area (the hippocampus) occurring well into adulthood. This process contributes to many species’ capacity to learn, remember and regenerate. However whether this process occurs in humans is heavily debated. Using new neuroscience tools, this project will produce new insights into human adult neurogenesis by deeply examining hippocampal cells that express the newborn cell marker, doublecortin. This will enable clarification of the existence and extent of adult neurogenesis in humans, and provide the foundation to leverage this process for improving learning, memory and brain regeneration in people.Read moreRead less
Afferent stimulation-induced plasticity and its functional significance. Certain regions of the brain can reorganise (plasticity) during motor learning or when there is damage to peripheral nerves or muscles. There is a large body of evidence for these plastic changes in animals. Until recently data showing that similar changes occurred in humans was limited. However, we have recently demonstrated that certain patterns of peripheral stimulation can indeed induce similar changes in human subjects ....Afferent stimulation-induced plasticity and its functional significance. Certain regions of the brain can reorganise (plasticity) during motor learning or when there is damage to peripheral nerves or muscles. There is a large body of evidence for these plastic changes in animals. Until recently data showing that similar changes occurred in humans was limited. However, we have recently demonstrated that certain patterns of peripheral stimulation can indeed induce similar changes in human subjects. These findings are important for our understanding of the mechanisms of motor control and learning.Read moreRead less
Old brain cells perform new tricks to allow life-long learning. In the brain, nerve cells transmit electrical signals more quickly and reliably when they are insulated. The insulating cells undergo small adaptive changes that speed up information transfer during learning, and the faster the electrical signal, the better the learning outcomes. This project aims to understand the signals that direct insulating cells to adapt and support life-long learning. In the longer term, this knowledge may be ....Old brain cells perform new tricks to allow life-long learning. In the brain, nerve cells transmit electrical signals more quickly and reliably when they are insulated. The insulating cells undergo small adaptive changes that speed up information transfer during learning, and the faster the electrical signal, the better the learning outcomes. This project aims to understand the signals that direct insulating cells to adapt and support life-long learning. In the longer term, this knowledge may be used to: develop interventions that improve learning and educational outcomes; counteract age-related memory decline and enable longer work force participation; develop strategies to circumvent the memory loss caused by brain diseases, or improve the design of computer hardware.Read moreRead less
Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly qui ....Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly quiescent, dividing rarely to ensure that they are not prematurely exhausted. However, the factors that maintain this quiescence are very poorly defined. The project aims to understand how stem cell quiescence is controlled at both a molecular and cellular level in vivo within the adult mouse brain.Read moreRead less
Transcriptional regulation of brain size during development. This project aims to understand the fundamental mechanisms through which intermediate progenitor cell (IPC) formation is regulated within the cerebral cortex. The cerebral cortex plays a key role in functions central to our existence, including emotion, behaviour, learning and memory. During development, cortical neural stem cells produce neurons via IPCs. This project expects to discover the genetic programs regulating neuronal produc ....Transcriptional regulation of brain size during development. This project aims to understand the fundamental mechanisms through which intermediate progenitor cell (IPC) formation is regulated within the cerebral cortex. The cerebral cortex plays a key role in functions central to our existence, including emotion, behaviour, learning and memory. During development, cortical neural stem cells produce neurons via IPCs. This project expects to discover the genetic programs regulating neuronal production, providing significant conceptual advances in this key field. This will provide significant benefits, such as enhancing our understanding of how overall brain size is regulated during development.Read moreRead less