Understanding Cortical Circuitry Underlying Sensory Integration And The Consequence Of Its Developmental Disruption
Funder
National Health and Medical Research Council
Funding Amount
$527,395.00
Summary
The mammalian neocortex is organised into six layers with a systematic pattern of wiring that relies on normal development and balanced activity of neurons. This project combines developmental, electrophysiological, optogenetic behavioural, and computational methods to establish how the properties of the precise structure of cortical circuits impact their function and how disruptions in the balanced activity during development affect circuit formation and function in the mature brain.
Dopamine Neuron Ontogeny: Convergent Neurobiological Pathway For Risk Factors Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$337,214.00
Summary
Schizophrenia is associated with changes in dopamine (a signalling molecule in the brain). These changes are present prior to psychosis, suggesting they begin early in development. Our aims are to manipulate key factors in the development of brain dopamine systems to clarify their role in psychosis and schizophrenia. This work has the potential to identify early brain changes that lead to schizophrenia, which in turn may generate better diagnoses and outcomes for people with this disorder.
The Role Of Meninges In Midbrain Dopamine Development
Funder
National Health and Medical Research Council
Funding Amount
$378,311.00
Summary
Dopamine neurons are important for the control of movement, emotion and cognitive function, and are affected in a number of disorders such as Parkinson’s disease. Instrumental in improving our knowledge of disease etiology and the development of new therapies will be a greater understanding of how these cells are initially born during development. This project examines the role of the brain’s meninges in dopamine development and repair and will identify proteins and signaling pathways involved.
Delayed Radial Glial Maturation Linked To NFI Deficiency As An Underlying Cause Of Cortical Defects In Humans And Mice
Funder
National Health and Medical Research Council
Funding Amount
$801,979.00
Summary
The timely generation of neurons and glia is important for brain development and consequently brain function throughout life. Nuclear factor I (NFI) genes are important for regulating the production of neurons and glia, and people with disrupted NFI genes have severe cognitive and motor deficits. Using human genetic data and mouse models, we will analyse how disrupting these genes affects brain development, and changes the overall structure and wiring of the cerebral cortex as well as behaviour.
Normal And Abnormal Development Of Brain Wiring And Its Impact On Brain Function
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
My laboratory is striving to understand how the patterns of neuronal connections form in the developing brain and how these underpin the functions of the brain throughout life. We use high-field magnetic resonance imaging to measure brain wiring and we investigate the genetic and environmental mechanisms causing developmental brain disorders that result in intellectual disability, autism, epilepsy and some mental illnesses.
Knowledge, Identification And Exploitation Of Dopaminergic Axon Guidance Cues Will Improve Cell Replacement Therapy For ParkinsonÍs Disease.
Funder
National Health and Medical Research Council
Funding Amount
$481,797.00
Summary
Many obstacles exist for cell transplantation in ParkinsonÍs Disease; namely poor graft survival, restoration of appropriate circuitry and adequate nerve fiber growth from new cells. Using knowledge of how neural circuits are established during fetal development, we will attempt to recapitulate these events following transplantation. Further, we will identify new and novel cues in regulating the connectivity and growth of these nerve fibers.
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
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.
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
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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