Regulation Of Brain Development By Members Of The Fibroblast Growth Factor Family
Funder
National Health and Medical Research Council
Funding Amount
$65,685.00
Summary
The brain is the most complex organ in the body. It is made up of many different types of cells broadly classified into two classes called neurons and glia. The growth of the brain from a small population of immature neuroepithelial cells to many different types of neurons and glia is controlled by small potent proteins called growth factors. We understand that many different families of growth factors are involved in the development of the brain but not how they do what they do. We are studying ....The brain is the most complex organ in the body. It is made up of many different types of cells broadly classified into two classes called neurons and glia. The growth of the brain from a small population of immature neuroepithelial cells to many different types of neurons and glia is controlled by small potent proteins called growth factors. We understand that many different families of growth factors are involved in the development of the brain but not how they do what they do. We are studying the members of one particular family known as the Fibroblast Growth Factor family or FGFs. We want to find out how they instruct young brain cells to grow and divide and turn into mature neurons.Read 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
Characterisation Of Neuregulin-2 Function In The Nervous System.
Funder
National Health and Medical Research Council
Funding Amount
$183,250.00
Summary
The Neuregulins (NRG's) are a family of four structurally related growth factors expressed in the developing and adult brain. NRG-1 is essential for life and has been implicated in the development and maintenance of both neurons and glial cells, as well as being essential for normal heart formation. NRG-2 was identified by us and others as being closely related to NRG-1 and, like NRG-1, it is also expressed predominantly in neuronal populations of the brain. One striking feature of NRG-2 express ....The Neuregulins (NRG's) are a family of four structurally related growth factors expressed in the developing and adult brain. NRG-1 is essential for life and has been implicated in the development and maintenance of both neurons and glial cells, as well as being essential for normal heart formation. NRG-2 was identified by us and others as being closely related to NRG-1 and, like NRG-1, it is also expressed predominantly in neuronal populations of the brain. One striking feature of NRG-2 expression in the adult brain is its localisation to regions associated with neurogenesis (renewal of neurons from stem cell precursors). Outside the nervous system Neuregulin-2 can stimulate the proliferation and differentiation of epithelial cells. However, little is known about the activity of Neuregulin-2 in the brain. This grant proposal aims to study the biological functions of Neuregulin-2 in the developing and adult central nervous system. The experimental design is based on characterisation of mice that do not contain the Neuregulin-2 gene. We will also look specifically at the action of Neuregulin-2 on discrete populations of neuronal cells, grown in tissue culture. We expect that these studies will provide valuable insight into the role of NRG-2 in the brain and that they will be the basis for defining the mechanisms by which NRG-2 activity differs to that of the NRG family members. By studying factors that are involved in the development of the nervous system it is hoped that valuable insights will be made regarding repair and regeneration in the adult brain.Read moreRead less
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.
Brain Plasticity Following Changes In Sensory Input
Funder
National Health and Medical Research Council
Funding Amount
$312,576.00
Summary
The research proposed here will investigate the mechanisms our brains use to adapt to changes in sensory input, as occurs following blindness, deafness, nerve damage or loss of a limb. The information gathered will help develop treatments for diseases associated with sensory loss, as well as those associated with deficits in our ability to learn and remember, such as Alzheimer's disease.
Suppressor Of Cytokine Signalling-2 (SOCS2) And Its Role In Neuronal Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron or another cell type, such as a glial cell and so we are ....Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron or another cell type, such as a glial cell and so we are examining factors which influence this process, which is called differentiation. Growth factors are important mediators of this process and suppressor of cytokine signalling (SOCS) proteins are important in determining how cells respond to growth factors. The overall aims of this project are to determine the role that SOCS genes and in particular, SOCS2 play in neural stem cell differentiation into neurons and glia, neuron process outgrowth and neuronal and glial injury responses in the nervous system. This will be examined in normal cells and cells which over-express or do not express SOCS2 genes. Understanding the biology of neural growth factor responsiveness may eventually allow us to devise therapeutic strategies for use following brain-spinal injury or disease, including generation of neurons from stem cells.Read moreRead less
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
Development And Refinement Of Neural Connections In The Adult Brain In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,061,596.00
Summary
Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a ....Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in partnership with the biopharmaceutical industry.Read moreRead less