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.
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.
Mechanisms Of PTEN Regulation By Ndfip1 And Their Biological Consequences For Neuron Survival During Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$686,640.00
Summary
We have discovered a new protein (Ndfip1) that protects brain cells from death after brain injury from trauma and stroke. We will investigate why this protein is activated only in some, but not in other, brain cells after injury. In this application, we will study the mechanisms behind neuron protection, and use this information to explore how to increase the number of brain cells activating Ndfip1.
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
Proteases And Protease-inhibitor Complexes As Modulators Of Traumatic Brain Injury Severity
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Traumatic brain injury (TBI) is a significant cause of mortality and morbidity in Australia, affecting approximately 21,800 Australians annually. A large number of survivors have permanent neurological deficits, causing adverse effects on lifestyle and family relationships and placing a significant burden on the health system. In this project we will address a novel means to improve TBI outcome by targeting two linked enzyme systems that together have been shown to be deleterious in this conditi ....Traumatic brain injury (TBI) is a significant cause of mortality and morbidity in Australia, affecting approximately 21,800 Australians annually. A large number of survivors have permanent neurological deficits, causing adverse effects on lifestyle and family relationships and placing a significant burden on the health system. In this project we will address a novel means to improve TBI outcome by targeting two linked enzyme systems that together have been shown to be deleterious in this condition.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.
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.
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.
The amygdala is a region of the brain involved in assinging emotional salience to our sensory world. Disorders of amygdala function lead to a range of anxiety related disorders. In this grant we aim to understand the neural circuits that are invovled in one form of learning that engages the amygdala - fear conditioning.