An Integrated “omic” Approach To Neurodevelopmental Disorders Using Disease-discordant Monozygotic Twins
Funder
National Health and Medical Research Council
Funding Amount
$84,800.00
Summary
This project targets neurodevelopment disorders such as autism spectrum disorder, cerebral palsy and epilepsy and focuses on studying the environmental factors (epigenetics) affecting the disease mechanisms in these disorders. The study will be performed on twin samples and will help in the diagnosis of the disease risk at an earlier stage. It will also help to understand the causes of these important neurological diseases.
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.
Investigating Secondary Effects Of BACE1 Inhibition, A Promising Therapy For Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$700,672.00
Summary
Synapses transfer information between neurons in the brain. In Alzheimer’s disease (AD), synapse loss results in dementia therefore it is imperative that any potential therapeutic drugs do not inadvertently cause further synapse loss. Drugs aimed at blocking production of toxic protein fragments in AD might have adverse secondary effects on synapse development and function. This research will determine whether this is the case and inform new therapeutic approaches aimed at minimizing side effect ....Synapses transfer information between neurons in the brain. In Alzheimer’s disease (AD), synapse loss results in dementia therefore it is imperative that any potential therapeutic drugs do not inadvertently cause further synapse loss. Drugs aimed at blocking production of toxic protein fragments in AD might have adverse secondary effects on synapse development and function. This research will determine whether this is the case and inform new therapeutic approaches aimed at minimizing side effects.Read moreRead less
Properties And Functions Of Reactive Astrocytes And Their Role In Neurological Disease
Funder
National Health and Medical Research Council
Funding Amount
$344,652.00
Summary
I am a developmental neuroscientist interested in the way alterations to normal brain development affect neuronal function later in life. I intend to investigate this by studying astrocytes – the cells that support and nourish brain nerve cells. In some diseases these astrocytes become stressed and instead of aiding the brain, set about destroying it. A better understanding of their action during development and disease may enable improved interventions for the treatment of many brain disorders.
Controlling The Development And Function Of Hindbrain Commissures In Vertebrate Animals: The Role Of Robo3 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$393,834.00
Summary
Commissural axons connect and coordinate activity between neurons of the left and right sides of the central nervous system. In the forebrain, formation of commissural axons is determined by guidance factors at the midline between the two hemispheres, and abnormalities in guidance can cause developmental malformations. The aims of this project are to elucidate function of the Robo/Slit family of molecules in regulating axon guidance of commissural neurons, particularly in the corpus callosum.
Compromised Fetal Brain Development: Neurogenesis And The Potential For Therapeutic Intervention.
Funder
National Health and Medical Research Council
Funding Amount
$497,280.00
Summary
Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and ....Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and nutrient levels during pregnancy) that there is a reduction in neurons and in the connections between them. This may result from a reduction in number of newly generated neurons (neurogenesis), or an increase in neuronal death (apoptosis), or both. To develop therapeutic strategies to improve brain growth and ultimately functional recovery, we must understand the mechanisms which lead to these brain changes. In this project, we will use our guinea pig model to: 1) determine whether a suboptimal fetal environment decreases neuronal numbers by influencing neurogenesis, apoptosis or both, 2) study changes in the compromised brain environment which are likely to influence apoptosis and neurogenesis, 3) determine whether a suboptimal fetal environment has long-term effects on adult neurogenesis and 4) determine whether treatment with erythropoietin (Epo), a naturally occurring hormone, can resolve deficits in brain development and function. Epo is an exciting candidate as it is, or is in the process of being used to treat stroke and newborn asphyxiation. Epo has also been shown to prevent neuronal death and promote neurogenesis following brain injury. Understanding the mechanisms and finding effective treatments for brain damage is a vital area of endeavour if we are to help infants develop their maximum potential and reduce the enormous social, economic and educational burden which must be borne by the individual and society in general when things go wrong during pregnancy.Read moreRead less
The Role Of Netrin-DCC In The Development Of The Corpus Callosum
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with ove ....During embryonic development neurons send out axons that connect to other target neurons within the brain. The proper connectivity of these axons is vital to brain function. The largest axon tract in the brain is called the corpus callosum and connects neurons in the left and right cerebral hemispheres. When the corpus callosum does not form, significant cognitive, motor and sensory deficits occur in patients. This condition, known as agenesis of the corpus callosum (ACC), is associated with over 50 different human congenital syndromes. Thus understanding how the genes and molecules involved in the formation of the corpus callosum function in normal development can provide the basis for our understanding of what goes wrong in ACC. In this proposal we will investigate the role of the axon guidance molecule Netrin1, and its receptor DCC, in development of the corpus callosum in both a mouse model and in humans with malformations of the corpus callosum. Although Netrin1-DCC signalling has traditionally been associated with mechanisms of axon guidance, we hypothesize that these molecules may play a different role, specifically in cellular adhesion and ultimately in the fusion of the two cerebral hemispheres, in a manner that allows the corpus callosum to form. A second role for Netrin1-DCC signalling may be in the guidance of these axons once the midline has fused correctly and we investigate this in Aim 2 of the proposal. Finally, we are collaborating with a paediatric neurologist at UCSF, who has identified several mutations in the DCC gene in patients with ACC. In Aim 3 we test whether these mutations disrupt the function of DCC in callosal axon pathfinding. Understanding how these genes function during development of the brain and how their function may be altered in ACC is crucial to providing a proper diagnosis and prognosis for these patients. Ultimately, understanding more about how these genes function could also lead to prevention of these disorders.Read moreRead less
Genetic And Functional Analysis Of Brain Malformations
Funder
National Health and Medical Research Council
Funding Amount
$105,327.00
Summary
Disorders of early brain development are recognised as a significant cause of illness and disability in children. Unfortunately, the causes of these conditions are poorly understood, and treatment options are limited. It has become apparent that many of these conditions have an underlying genetic basis. This project will identify genes that regulate brain development and aid the development of improved treatment programs for brain and mind disorders.
Dopamine-2 Receptor Antibody In Movement And Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$415,783.00
Summary
Autoimmune movement and psychiatric disorders are a common cause of neurological disability young adults and adolescents. We have identified a subgroup of patients whose disease is associated with an autoimmune reaction. Our study will identify the earliest immune responses against the brain in children with autoimmune movement and psychiatric disorders. Identifying these early immune responses will allow early and directed treatments to prevent disability and death in the future.
Neourobiology Of Human Epilepsy: Genes, Cellular Mechanisms,network And Whole Brain
Funder
National Health and Medical Research Council
Funding Amount
$17,652,824.00
Summary
The team is comprised of neurologists, molecular geneticists, physiologists and brain imaging specialists and leads the world in the discovery of the genetic causes of epilepsy. They will continue to identify genes underlying epilepsy and study how genetic variations result in development of seizures. Advanced brain imaging will be used to understand the effects of genetic variation on brain structure and function. This study may lead to new diagnostic methods and treatments for epilepsy.