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.
Understanding The Molecular Basis Of Central Nervous System Myelination
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Oligodendrocytes are the cell type in the central nervous system that produce myelin, the insulating layer around nerve cells. Loss of oligodendrocytes and myelin are key features of multiple sclerosis. This project aims to clarify the mechanisms that control the myelination of nerve cells during normal development, allowing the development of strategies to promote myelin repair in human diseases such as Multiple Sclerosis.
Investigating Underlying Mechanisms Linking Type 2 Diabetes With Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$701,950.00
Summary
With type-2 diabetes representing a major risk factor for neurodegenerative diseases such as Alzheimer's disease, it is important to understand the underlying mechanisms. This project will provide significant insight into how T2D impacts the brain with a focus on how deficiencies in brain inuslin signaling drives neurodegeneration. We will also evaluate novel inuslin like molecules at improving brain insulin siganling and preventing or slowing down the neurodegenerative process.
Neuron To Glia Signalling: Learning How Synaptic Signalling Can Promote CNS Remyelination
Funder
National Health and Medical Research Council
Funding Amount
$609,650.00
Summary
An immature cell type in the brain, known as the oligodendrocytes progenitor cell (OPC), receives direct electrical communication from neurons. This communication regulates the behavior of the OPC, affecting its ability to divide and generate new brain cells. This project will identify the signaling molecules that guide the OPC to for this specialized contact with the nerve cell. Understanding this communication has important implications for the treatment of Multiple Sclerosis.
Assessing The Role Of The N-terminus Of The Prion Protein, Emphasising Constitutive Cleavage, In Normal Function And Pathogenesis, As Well As Defining The Relationship Between Intensity Of Surveillance And Sporadic CJD Incidence.
Funder
National Health and Medical Research Council
Funding Amount
$387,469.00
Summary
As a neurologist undertaking research into prion diseases over an extended period, I have been able to lead and participate in many projects that have made significant contributions, such as validation of new diagnostic tests for Creutzfeldt-Jakob disease (CJD), assessment of potential therapeutics, provide insights into the normal function of the prion protein and the underlying pathways causing cellular damage and determine the real significance of apparent clusters of sporadic CJD.
The Role Of BMP Signalling During Chronic Demyelination And Myelin Repair
Funder
National Health and Medical Research Council
Funding Amount
$67,381.00
Summary
Multiple sclerosis (MS) is the most common neurodegenerative disease affecting young adults. It is a disease that kills myelin cells, which are important support cells for neurons and critical for neuronal function. This research investigates the role of a specific signaling pathway with respect to myelin cell production and repair with the ultimate aim of identifying regenerative therapeutics for MS.
Sez-6 Signalling Mechanisms And Function In The Developing Neocortex
Funder
National Health and Medical Research Council
Funding Amount
$501,815.00
Summary
Over the course of evolution, the mammalian brain cortex has become disproportionately large with respect to other brain regions. The dramatic increase in processing power resulting from the increased neuronal number and connectivity in the cortex has enabled us to acquire functions that make us human, such as the use of language. In spite of the enormous difference in size between the brains of humans and those of mice, studies on cortical development in mice are relevant to humans since the or ....Over the course of evolution, the mammalian brain cortex has become disproportionately large with respect to other brain regions. The dramatic increase in processing power resulting from the increased neuronal number and connectivity in the cortex has enabled us to acquire functions that make us human, such as the use of language. In spite of the enormous difference in size between the brains of humans and those of mice, studies on cortical development in mice are relevant to humans since the organization of the cortex (thickness, layer patterning and regional specialization) is very similar in these two organisms, and indeed, in all mammals. A complex series of developmental events is required to produce a normal brain cortex. Malformations in the cortex occurring in human neurological disorders, including epilepsy and mental retardation, result from mutations in genes regulating crucial developmental processes. Failure of developing nerve cells to make the correct connections can result in these, or other, debilitating neurological conditions. We have evidence that a brain protein called Seizure-related gene 6 (Sez-6) regulates normal connectivity and function of neurons in the mature cortex. We will determine the molecular pathways used for signalling of Sez-6 and also investigate in detail the formation of connections between cortical neurons early in development and how these connections become aberrant in the absence of Sez-6 function.Read moreRead less
The Role Of Down Syndrome Candidate Region 1 (DSCR1) In Neurotransmitter Release, Vesicle Recycling And Down Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$352,318.00
Summary
Individuals with Down syndrome (DS) have three copies of human chromosome 21 (HSA21), rather than the normal two. The symptoms observed in DS individuals are therefore due to the overexpression of HSA21 genes. Since all individuals with DS develop symptoms in the brain similar to those see in Alzheimer's disease (AD), there may be a common mechanism that can be traced to the extra gene dosage from HSA21. We are interested in one of these genes, Down syndrome candidate region 1 (Dscr1), which is ....Individuals with Down syndrome (DS) have three copies of human chromosome 21 (HSA21), rather than the normal two. The symptoms observed in DS individuals are therefore due to the overexpression of HSA21 genes. Since all individuals with DS develop symptoms in the brain similar to those see in Alzheimer's disease (AD), there may be a common mechanism that can be traced to the extra gene dosage from HSA21. We are interested in one of these genes, Down syndrome candidate region 1 (Dscr1), which is overexpressed in both DS and AD brains. We hypothesise that Dscr1 has a role in regulating exocytosis, a process in which chemical messengers are released from cells. Exocytosis is highly specialised in the brain where neurotransmitters are released from neuronal synapses in a process known as synaptic transmission. Reduced synaptic transmission is one of the earliest hallmark of DS and AD occurring long before the classical neurological traits of DS and AD such as plaque formation and dementia. We propose that alterations in Dscr1 expression are responsible for the reduced neuronal exocytosis observed in the early stages of DS and AD. We have generated mice in which Dscr1 expression is altered, as occurs in DS and AD brains, and our preliminary studies indicate that exocytosis is reduced in these mice. We now wish to find the intracellular changes responsible for regulating exocytosis when Dscr1 expression is altered. We also aim to compare this to exocytosis in classical DS mouse models which have an extra chromosome 21 and in similar DS mouse models which have normal levels of Dscr1. This project will uncover the currently unknown functions of Dscr1 in exocytosis in an animal model, allow us to gauge whether Dscr1 is solely responsible for altering exocytosis in DS amongst other HSA21 genes, enable us to better understand the mechanisms initiating DS and AD and possibly lead to new targets of early intervention in these diseases.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