Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting ....Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting them in mice, testing for developmental, cognitive and motor effects, and characterising the structures with which they are associated. The results of the project are expected to open new vistas in neuroscience, contributing to understanding the molecular basis of brain function and the 'dark matter' of the genome.Read moreRead less
Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during developmen ....Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during development, test whether synaptic activation of receptors is required for these changes and define the pattern of activity-dependent changes in gene expression necessary for developmental changes in synaptic transmission. Understanding this interaction between synaptic phenome and activity-dependent genomic expression will expand our understanding of brain development and function.Read moreRead less
Memory and the temporal lobes. This project will use brain imaging techniques to investigate how humans perceive, combine and access stored knowledge about the world via different senses. This information will not only provide information on normal brain processes, but will also provide vital data on what happens to memory if certain regions of the brain become damaged.
Dopaminergic mechanisms of visual selective attention in the fly. What we pay attention to guides our behaviour. There is increasing evidence that even the smallest animals, such as insects, have a selective attention. Neuromodulators such as dopamine (DA) regulate general arousal states in flies as well as humans, but it is not well understood how DA modulates selective attention. This project will genetically manipulate DA in the fly Drosophila in order to study its role in visual selective at ....Dopaminergic mechanisms of visual selective attention in the fly. What we pay attention to guides our behaviour. There is increasing evidence that even the smallest animals, such as insects, have a selective attention. Neuromodulators such as dopamine (DA) regulate general arousal states in flies as well as humans, but it is not well understood how DA modulates selective attention. This project will genetically manipulate DA in the fly Drosophila in order to study its role in visual selective attention, by: examining neural circuits; attention behaviour; and, brain recordings. Our work will reveal whether DA mainly controls general responsiveness levels, or whether DA is also involved in coordinating attention dynamics. This study has important implications for understanding attention disorders.Read moreRead less
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.
Neural mechanisms of attention in the honeybee and Drosophila melanogaster. By examining convergent neural mechanisms of attention in insects and comparing these mechanisms to those found in vertebrates, we may uncover basic principles of how attention operates in widely divergent systems. This type of basic scientific research could be used to provide a framework to develop better approaches for treatment for individuals with defects in attention. Such defects are symptoms of several psycholo ....Neural mechanisms of attention in the honeybee and Drosophila melanogaster. By examining convergent neural mechanisms of attention in insects and comparing these mechanisms to those found in vertebrates, we may uncover basic principles of how attention operates in widely divergent systems. This type of basic scientific research could be used to provide a framework to develop better approaches for treatment for individuals with defects in attention. Such defects are symptoms of several psychological conditions, including attention deficit disorder, autism, and schizophrenia, which have major social and economic costs in Australia. Therefore, by expanding our understanding of how attention operates at the level of neurons, we can begin to develop targeted treatments for addressing these conditions. 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
Investigating the Molecular Mechanism of Synaptic Transmission. This project aims to increase our understanding of the synaptic function of the nervous system. Neurons communicate with each other via the release of neurotransmitters at specialised structures known as synapses. Synaptic vesicle (SV) release from the presynaptic neuron is essential for this neuronal transmission, which drives all aspects of nervous system function, including behaviour and cognition. This project plans to investiga ....Investigating the Molecular Mechanism of Synaptic Transmission. This project aims to increase our understanding of the synaptic function of the nervous system. Neurons communicate with each other via the release of neurotransmitters at specialised structures known as synapses. Synaptic vesicle (SV) release from the presynaptic neuron is essential for this neuronal transmission, which drives all aspects of nervous system function, including behaviour and cognition. This project plans to investigate how key synaptic proteins and the interactions between them regulate spontaneous SV release. It aims to reveal the molecular mechanism of both basal level regulation and the potentiation of spontaneous SV release, using a Caenorhabditis elegans model system.Read moreRead less
Dendritic information processing during sensory-motor behaviour. The neocortex is centrally involved in the control of animal behaviour. It is largely unknown how neocortical neurons contribute to the neuronal computations that generate behaviour. The project will study how individual neurons in the neocortex compute the sensory and motor signals that underlie an important exploratory behaviour in rodents.
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