Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can ....There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can be used to assist in trying to modulate and facilitate directed regrowth following injury.Read moreRead less
Post Synaptic Density Scaffold Proteins In The Growth Cone: Homer And Shank, Crucial For Calcium Signaling.
Funder
National Health and Medical Research Council
Funding Amount
$237,909.00
Summary
Our brain is a complex, yet precise electrical circuit. Understanding how the embryonic brain is wired has direct implications for all aspects of life, from the growing foetus in mother's womb, to learning algebra and for maintaining the active memories of our ageing population. This project aims to provide new insight into understanding how the embryonic brain is wired, crucial information for future pharmacological or gene therapy approaches to mental illness, ageing, and neuronal injury.
Characterisation Of Neural Stem Cells In The Ageing Mammalian Brain
Funder
National Health and Medical Research Council
Funding Amount
$182,411.00
Summary
Due to their relatively recent discovery, little is known about how stem cells in the brain are affected by age. This work will initially focus on understanding how age affects the number of stem cells found in the brain, and how their normal function and regenerative capacity are compromised with increasing age. The second phase of this study will examine how we can slow or even reverse these age-related changes on stem cells by environmental manipulation.
Neogenin Regulates Progenitor Division And Interneuron Migration In The Developing Forebrain
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
In humans, mutations in genes controlling the production of new neurons in the embryonic brain result in severe disruption of the adult cortex. This project tests the hypothesis that one cell surface molecule, Neogenin, regulates the birth of new neurons and their subsequent travels through the developing brain to form the neocortex. The outcome of these studies will provide fundamental insights into the aberrant processes that underlie human mental retardation, epilepsy, dyslexia and autism.
Identification And Origin Of Neuronal Precursors In The Adult Mouse Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$284,250.00
Summary
It is now clear that new neurons continue to be generated under normal conditions in at least 2 regions of the adult mammalian brain: the olfactory bulb (smell centre) and the hippocampus (organ responsible for memory and learning). These new neurons replace those lost as part of aging and, as such, are vital to normal brain function. Recently, these results have been extended to show that various insults, such as stroke, can cause the proliferation of precursor cells in the adult brain, which u ....It is now clear that new neurons continue to be generated under normal conditions in at least 2 regions of the adult mammalian brain: the olfactory bulb (smell centre) and the hippocampus (organ responsible for memory and learning). These new neurons replace those lost as part of aging and, as such, are vital to normal brain function. Recently, these results have been extended to show that various insults, such as stroke, can cause the proliferation of precursor cells in the adult brain, which ultimately results in the addition of new nerve cells that go on to repair the pathological damage. Although the production of new nerve cells under normal conditions and following damage is highly significant, we still know surprisingly little about the nature of the precursor population which produces these cells and even less about their regulation. For the most part, this has been due to our inability to identify and isolate the brain stem cell. Thus, over the last 5 years I have adapted cell sorting techniques - which are normally used to separate blood cells to isolate populations of cells from the brains of adult mice. As a result of my work, we are now in the position to sort for a population of stem cells that are known to give rise to new brain cells in the adult olfactory bulb. This work will be extended to identify and characterise the precursor population that resides in the hippocampus. The identification of this hippocampal precursor population will thus provide the foundation for developing new approaches for the treatment of diseases such as strokeRead moreRead less
Dissecting The Molecular Mechanisms Driving Cell Migration During Neurulation Triggered By The Netrin Receptor, Neogenin
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
In humans, abnormalities in brain and spinal cord formation during early embryogenesis result in congenital syndromes such as spina bifida and anencephaly. These defects occur at a rate of 1-1000 pregnancies and are therefore a major contributor to pre- and perinatal deaths. In the early embryo, the brain and spinal cord begin as a hollow tube of cells (the neural tube) that subsequently expands into the complex structures seen at birth. It is known that the neural tube is formed by a complex pr ....In humans, abnormalities in brain and spinal cord formation during early embryogenesis result in congenital syndromes such as spina bifida and anencephaly. These defects occur at a rate of 1-1000 pregnancies and are therefore a major contributor to pre- and perinatal deaths. In the early embryo, the brain and spinal cord begin as a hollow tube of cells (the neural tube) that subsequently expands into the complex structures seen at birth. It is known that the neural tube is formed by a complex process in which early neural cells migrate toward the midline of the embryo and subsequently coalesce. This project seeks to determine the function of one molecular signaling pathway (the neogenin pathway) that has been implicated in driving these cell migration events. We will initially use the frog, Xenopus laevis, as our embryonic model since the developmental processes that form the Xenopus neural tube closely parallel those ocurring in the human embryo. This model will allow us to identify the molecules in the neogenin signaling pathway. We will also create mice that carry a mutation in the neogenin gene so that we can study neogenin function in the mammal. We anticipate that these studies will provide important insights into the development of the central nervous system and also into the aberrant molecular processes underlying neural tube defects in man.Read moreRead less