SEZ6 AND NEURONAL CALCIUM SIGNALLING IN SYNAPSE DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$617,685.00
Summary
Inappropriate development and function of neuronal circuits is a universal feature of neurological disorders of cognition such as Down syndrome, autism spectrum disorders and Fragile X mental retardation, epilepsy, schizophrenia and Alzheimer�s disease. In these diseases, neurons exhibit abnormal neuronal branches (dendrites) and abnormal connections on dendritic spines. This research is aimed at understanding the mechanisms controlling dendrite development that underpin proper neuronal wiring.
The neocortex is the region of the brain that underlies all cognitive functions. Mental disorders, such as schizophrenia, occur when the communication between nerve cells in the neocortex breaks down. We propose to make electrical measurements from the thin processes of neurons that receive input from widely separated neocortical areas to understand how areas of the neocortex are functionally interlinked, with the ultimate aim to identify how these processes are disturbed in mental disorders.
Understanding The Embryonic Origins Of Cortical Malformations
Funder
National Health and Medical Research Council
Funding Amount
$815,228.00
Summary
Cortical malformation leads to mental retardation and epilepsy. Identification of the aberrant developmental processes contributing to these devastating syndromes is essential for accurate clinical assessment and development of novel therapeutics. Here we investigate a developmentally important receptor, Neogenin, which when mutated, leads to cortical malformations. Determining how Neogenin functions is expected to uncover new signaling pathways contributing to these malformations.
Discovering Molecules And Mechanisms Regulating Dendrite Formation
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
Dendrites are neuronal projections necessary to receive stimuli from other neurons or the external environment. Abnormalities in dendrite development associate with mental retardation and other human conditions such as Down syndrome, Rett syndrome and Fragile-X syndrome. The studies presented in this proposal, using the powerful genetic and molecular tools available for the nematode C. elegans, will provide new insight into the cellular and molecular mechanisms regulating dendrite development.
Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$330,735.00
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
Deciphering The Mechanisms Underlying LRP-mediated Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$370,659.00
Summary
Nerve damage can develop post injury or disease and are often very debilitating, slow to heal and cause increased pain. Our work aims to examine a new class of molecules that we show can activate selected fat-receptors on nerve cells to guide the growth of regenerating nerves. We will determine how these receptors function with the aim of developing a novel class of therapeutics directed at healing nerve damage.
Stimulation Of Neurogenesis By Growth Hormone To Improve Cognition In An Aged Animal Model Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$550,828.00
Summary
Production of new neurons in the hippocampus of adult animals plays a role in regulating learning and memory, and this production slows continuously with increasing age. Here we explore ways to activate dormant populations of neurogenic precursor cells in the hippocampus to produce new neurons. Since the precursor cells are still present in the hippocampus of an aged animal these studies will provide unequivocal evidence for their importance in reversing age-related cognitive decline and dementi ....Production of new neurons in the hippocampus of adult animals plays a role in regulating learning and memory, and this production slows continuously with increasing age. Here we explore ways to activate dormant populations of neurogenic precursor cells in the hippocampus to produce new neurons. Since the precursor cells are still present in the hippocampus of an aged animal these studies will provide unequivocal evidence for their importance in reversing age-related cognitive decline and dementia.Read moreRead less
A Comparative Study Between The Effects Of C-terminally Truncated A-synuclein Metabolites And Full Length A-synuclein In Aged Rat Hippocampal Neurons
Funder
National Health and Medical Research Council
Funding Amount
$231,284.00
Summary
I am a neurologist from Xi�an Jiaotong University, China. My major research interest is in neurodegenerative diseases, especially Parkinson and Alzheimer�s disease. I enter this field because I know ageing population will have an enormous impact on the world�s economy. I started collaboration with Dr. Weiping Gai in Flinders University. We are interested in the toxic effects of both a-synuclein and its metabolites, their mechanisms and ways to block them.
The Role Of Store-operated Calcium Entry In Neuronal Development
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Defects in brain development can manifest in a range of disorders including autism and mental retardation. The highly complex, precise network that is our nervous system forms during development. Our work will determine the role of key proteins in guiding developing neurons. Understanding the function of such proteins will improve our ability to predict the outcome caused by mutations in these proteins, in the developing foetus.
The Role Of TGFB1 In The Pathophysiology Of Late Stage Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$612,961.00
Summary
Schizophrenia is triggered in people with a genetic predisposition by as yet unknown environmental factors. Having shown that changes in gene expression in the brains of people with schizophrenia vary as the disease progresses, this application seeks to understand the changes in a pathway regulated by transforming growth factor ?1 that occur late in the progression of the illness. Understanding the changes in this important pathway could affect how people with schizophrenia are treated as their ....Schizophrenia is triggered in people with a genetic predisposition by as yet unknown environmental factors. Having shown that changes in gene expression in the brains of people with schizophrenia vary as the disease progresses, this application seeks to understand the changes in a pathway regulated by transforming growth factor ?1 that occur late in the progression of the illness. Understanding the changes in this important pathway could affect how people with schizophrenia are treated as their disorder progresses.Read moreRead less