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.
The Modulation Of Neuronal Activity By Inter-cortical Sensory Input
Funder
National Health and Medical Research Council
Funding Amount
$638,771.00
Summary
For any given behaviour, the brain must merge information from all different sensory systems to generate a coherent representation of the external world. How this is achieved is largely unknown and is the basis of this research proposal. Here, using cutting edge recording techniques, the activity of brain cells within the cortex will be measured during the activation of multiple sensory systems. This research will provide insight into therapeutic approaches to local brain damage.
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