THE ROLE OF UBIQUITIN LIGASE ADAPTOR PROTEIN NDFIP1 IN NEURONAL DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$581,813.00
Summary
Many brain diseases are characterized by faulty connections between nerve cells (neurons), in some cases caused by the inability to remove unwanted proteins from the neuron. This function is carried out by the ubiquitin-proteasome system (UPS). We have evidence that a UPS protein called Ndfip1 is important for forming functional brain circuits. We aim to discover whether neuron growth, branching and connectivity is promoted by Ndfip1 targeting of PTEN (phosphatase with tensin homology) to the UP ....Many brain diseases are characterized by faulty connections between nerve cells (neurons), in some cases caused by the inability to remove unwanted proteins from the neuron. This function is carried out by the ubiquitin-proteasome system (UPS). We have evidence that a UPS protein called Ndfip1 is important for forming functional brain circuits. We aim to discover whether neuron growth, branching and connectivity is promoted by Ndfip1 targeting of PTEN (phosphatase with tensin homology) to the UPS.Read moreRead less
DCC-Robo Interactions Cooperate To Regulate Callosal Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$383,422.00
Summary
In order for the brain to function, the correct connections between neurons must be formed during development. These connections, formed by the axonal processes of neurons, are able to find their synaptic targets by sensing molecular cues within the brain that guide them, by attraction or repulsion, to their target. This proposal investigates how attractive and repulsive signals are received and integrated in neurons to enable axons to find their targets in the brain.
Mechanisms Guiding Pathfinding And Positioning Of Cortical Interneurons
Funder
National Health and Medical Research Council
Funding Amount
$621,606.00
Summary
Brain disorders place an economic and social burden on Australia and the personal costs of these illnesses are immeasurable. Several brain abnormalities are caused from the failure of neurons to position themselves in the correct location when the brain develops. Our study aims to discover how neurons move and what factors influence this process. It provides an understanding of normal brain development, as well as providing insight into what may go wrong in the formation of brain diseases.
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
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Fibroblast Growth Factors In The Development Of Forebrain Commissures
Funder
National Health and Medical Research Council
Funding Amount
$497,796.00
Summary
In order to function correctly the two hemispheres of the brain must communicate information. This communication occurs across large fibre tracts called commissures. There are three commissural projections in the forebrain; the corpus callosum, the hippocampal commissure and the anterior commissure. Here we investigate the development of these commissures and provide a comprehensive analysis of the role of several secreted, fibroblast growth factor proteins, in their development.
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.
The Role Of The Zinc Finger Transcriptional Repressor Znf238 During Nerve Cell Maturation
Funder
National Health and Medical Research Council
Funding Amount
$394,264.00
Summary
Proper foetal brain assembly is critical for brain function, but the underlying genetic mechanisms remain poorly defined. In this study, I will investigate a family of proteins that “turn on” neural gene expression in combination with another protein that “turns off” their expression during nerve cell development. Understanding this novel on/off mechanism for controlling gene expression in newborn nerve cells will further our understanding of how the brain is assembled.
Wnt-Ryk Signaling In The Establishment Of Major Axon Tracts In The Embryonic Mouse Brain
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately 3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50 different human congenital syndromes have been described in which the corpus callosum does not form leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial for corpus callosum formation. This project aims to dissect that molecular mechanism ....The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately 3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50 different human congenital syndromes have been described in which the corpus callosum does not form leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial for corpus callosum formation. This project aims to dissect that molecular mechanisms controlling Ryk signaling during corpus callosum development. Our analysis of Ryk function will advance our understanding of the molecular mechanisms underlying the formation of this important commissure.Read moreRead less
How Can Trafficking Of The Tumour Suppressor PTEN Affect Normal And Abnormal Brain Development?
Funder
National Health and Medical Research Council
Funding Amount
$589,977.00
Summary
Autism is a complex neurodevelopmental disorder that is estimated to affect 1 in every 100 children. Currently we have no medical treatments to cure the disease. PTEN is a tumor suppressor that has been genetically linked to autism as it functions to inhibit cell growth that can result in abnormal brain development. In this grant we aim to study the location and function of PTEN and how failure of this system can result in neurodevelopmental diseases such as autism.