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
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.
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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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.
THE NEUROBIOLOGICAL BASIS OF INDIVIDUAL DIFFERENCES IN SUSCEPTIBILITY TO THE CONSEQUENCES OF STRESS
Funder
National Health and Medical Research Council
Funding Amount
$583,875.00
Summary
Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those t ....Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those that tend towards active coping strategies, such as attempting to take control of the situation. Previous studies have provided findings that suggest that passive coping is more common amongst sufferers of depression, post-traumatic stress disorder, and chronic pain syndrome than is active coping. But is this cause, or effect? And what are the intervening brain mechanisms? We attempt to address such questions in the present project using an animal model in which social conflict has been shown to trigger depression-like symptoms. In particular we wish to: (i) determine whether the patterns of brain activity triggered by social conflict are different for active vs. passive copers; (ii) determine whether the depression-like consequences of social conflict are more severe in passive than in active copers; (iii) determine whether differences in coping style and vulnerability to social conflict stress are due to the actions of a particular neurotransmitter, dopamine, in the prefrontal cortex of the brain; (iv) determine whether the actions of antidepressants might be attributable changes in prefrontal cortex dopamine function which in turn promote active coping in preference to passive coping. These studies will provide exciting new information about the neurobiological basis of individual differences in vulnerability to the harmful effects of stress, and thus will offer the hope of developing new ways of preventing devastating illnesses such as depression.Read moreRead less
LIM-homeodomain interactions in neuronal development. The loss of central nervous system function, through accident or disease, is devastating for affected individuals and their families. Our current inability to stimulate the regeneration of nervous tissue is a result of the lack of detailed knowledge of the complex processes that must take place, at the molecular and cellular levels, during neuronal development. We are determining how a group of cellular proteins that have key roles in motor n ....LIM-homeodomain interactions in neuronal development. The loss of central nervous system function, through accident or disease, is devastating for affected individuals and their families. Our current inability to stimulate the regeneration of nervous tissue is a result of the lack of detailed knowledge of the complex processes that must take place, at the molecular and cellular levels, during neuronal development. We are determining how a group of cellular proteins that have key roles in motor neuron development interact with each other and with DNA. With this information we are developing reagents that can be used to further probe central nervous system function and may ultimately be used to regenerate damaged nerves.Read moreRead less
Role Of Chemokines And Interferons In Neural Progenitor Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$521,178.00
Summary
Regeneration of the central nervous system following disease or injury is extremely limited and frequently results in substantial impairment. A potential therapy to replace damaged or killed nervous system cells is the use of neural stem cells. Neural stem cells are present in the central nervous system and frequently attempt, but fail to repair nervous system damage. This project aims to examine factors that regulate neural stem cell function including factors that may regulate their ability to ....Regeneration of the central nervous system following disease or injury is extremely limited and frequently results in substantial impairment. A potential therapy to replace damaged or killed nervous system cells is the use of neural stem cells. Neural stem cells are present in the central nervous system and frequently attempt, but fail to repair nervous system damage. This project aims to examine factors that regulate neural stem cell function including factors that may regulate their ability to migrate or become appropriate neural cell types. Of particular interest are factors known as chemokines that regulate cell migration as well as have a variety of other effects. In addition, interferons, which are inflammatory molecules present in the damaged nervous system and that we have shown affect neural stem cell function, may interact with chemokines and will also be examined. In addition to examining the effects of these factors on neural stem cells, the signalling pathways they use in these cells will also be determined.Read moreRead less
Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of ....Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of novel therapies that promote neuronal regeneration relevant for disorders such as spinal cord injury and Alzheimer's disease, which constitute a large socio-economic burden in Australia. Currently, 400 people contract spinal cord injury every year, corresponding to an annual cost of $1 billion, and more than 500 000 aging people suffer from Alzheimer's disease.Read moreRead less
Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe ....Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe the fundamental process of cell differentiation in the central nervous system.Read moreRead less