What shapes our brain? This project aims to improve our fundamental understanding of the biological mechanisms that drive folding of the cerebral cortex, which occurs during development of the brain. Cortical folding is unique to humans and higher mammals, and is thought to underpin the emergence of intelligence and contribute to higher-order brain functions. This project will enhance knowledge of how the cerebral cortex folds and develop novel tools for analysing brain development. The project ....What shapes our brain? This project aims to improve our fundamental understanding of the biological mechanisms that drive folding of the cerebral cortex, which occurs during development of the brain. Cortical folding is unique to humans and higher mammals, and is thought to underpin the emergence of intelligence and contribute to higher-order brain functions. This project will enhance knowledge of how the cerebral cortex folds and develop novel tools for analysing brain development. The project will provide significant benefits including the generation of fundamental knowledge with implications for future understanding of cortical folding abnormalities in babies born preterm, following fetal growth retardation in utero, or when exposed to maternal alcohol. In the longer term, the project will contribute to improvements to human neurodevelopment and brain health.Read moreRead less
Modelling human brain development with stem cells and biomaterials. With limited resources to directly study and advance our understanding of human neural development, this
proposal will establish models of 4 key stages. Employing innovative, interdisciplinary approaches, biomaterials will be fabricated to provide structural and chemical support for human stem cells during: (i) neural induction, (ii) specification into neuronal progenitor subpopulations, (iii) neuronal maturation and integration ....Modelling human brain development with stem cells and biomaterials. With limited resources to directly study and advance our understanding of human neural development, this
proposal will establish models of 4 key stages. Employing innovative, interdisciplinary approaches, biomaterials will be fabricated to provide structural and chemical support for human stem cells during: (i) neural induction, (ii) specification into neuronal progenitor subpopulations, (iii) neuronal maturation and integration into complex neural networks as well as, (iv) the organisation of neurons into larger 3-dimensional brain structures, namely folding of the human cortex. Further, biomaterials developed here have commercialisation potential, targeted at standardizing the culturing of human stem cells to defined neural populations.
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Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform o ....Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform of immediate use in the agriculture sector and for animal model alternatives. The benefit will be widespread, ensuring the growth and sustainability of our health and agriculture sector. The project will increase public understanding of protein delivery technologies, aiding in technology adoption.Read moreRead less
Subcellular recruitment of a RhoA ubiquitination complex by Rnd proteins. This study addresses a novel molecular mechanism through which members of the Rnd family of GTP-binding proteins regulate the morphology and migration of immature nerve cells of the developing nervous system. This study has broad implications for the understanding of cell migration during embryo development, as well as in health and disease.
Assessing the mechanisms and dynamics of myelination in the brain. This project is expected to refine our understanding of brain plasticity by revealing how myelin plasticity optimises brain function in response to experience. Using a multidisciplinary approach incorporating animal studies, mathematical modelling and computational neuroscience, the project seeks to redefine our understanding of myelin remodelling using an entirely new integrated cell-to-system approach. The expected outcome is f ....Assessing the mechanisms and dynamics of myelination in the brain. This project is expected to refine our understanding of brain plasticity by revealing how myelin plasticity optimises brain function in response to experience. Using a multidisciplinary approach incorporating animal studies, mathematical modelling and computational neuroscience, the project seeks to redefine our understanding of myelin remodelling using an entirely new integrated cell-to-system approach. The expected outcome is fundamental knowledge revealing how myelination is dynamically regulated by neural activity throughout life. This may transform current understanding of neuroplasticity that could aid in the future development of strategies to improve brain health.Read moreRead less
Modelling the human nervous system with human pluripotent stem cells. The human nervous system is one of the most complex structures evolved to date. In order to understand how it functions, and dysfunctions in a diseased state, it is fundamental to decipher how it develops to generate various neuronal populations that form this elaborate network. Human stem cells provide a valuable source to study such processes. The aim of this project is to use human stem cells to study how early progenitor c ....Modelling the human nervous system with human pluripotent stem cells. The human nervous system is one of the most complex structures evolved to date. In order to understand how it functions, and dysfunctions in a diseased state, it is fundamental to decipher how it develops to generate various neuronal populations that form this elaborate network. Human stem cells provide a valuable source to study such processes. The aim of this project is to use human stem cells to study how early progenitor cell types that structure the nervous system are generated and how their neuronal derivatives form connectivity and functional synapses. The outcome of these studies is that we will establish a cellular model of human neurogenesis that can be utilised to study developmental disease processes.Read moreRead less
A toxic cycle of inflammation and iron in the ageing brain. This project investigates why our brain cells gradually die as we grow older. We believe that infections and inflammation in other parts of the body cause iron to accumulate in the brain and become toxic. Iron supplements and ageing may make this situation worse. The results of this study could lead to new treatments for memory loss and dementia.
Development of sympathetic nerve pathways. The mature nervous system contains many types of neurons connected in precise ways. Developing neurons must make many decisions about what type of neuron to become and what connections to make. This study looks at the mechanisms that guide the developing neurons in these important decisions.
Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also mi ....Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. The planned data are likely to be relevant to other cell populations that also populate the areas through which they migrate, including neural crest-derived melanocytes and Schwann cell precursors.Read moreRead less
Wiring the gut's nervous system: formation and maturation of synapses. This project aims to determine how nerve circuits controlling intestinal functions develop; specifically how communication between specific nerve cells is established once they appear in the embryonic gut. It will fill a major hole in existing knowledge of mechanisms regulating the development of normal digestive behaviours.