The Role Of The Suppressors Of Cytokine Signalling 6 And 7 In Cerebral Cortex Development
Funder
National Health and Medical Research Council
Funding Amount
$377,189.00
Summary
Defects in neuronal cell migration during embryonic development lead to mental retardation and epilepsy. Although neuronal migration is essential for the development of normal intelligence, we know relatively little about the molecular mechanisms that regulate this process. We have identified two proteins, Socs6 and Socs7, which are essential for neuronal migration and normal cerebral cortex development. We propose to fully investigate the function of Socs6 and Socs7 during cortex development.
Neurodevelopmental Role Of Susceptibility Genes For Autism Spectrum Disorders: From Genes To Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$482,968.00
Summary
Autism is a developmental neuropsychiatric syndrome characterised by impairments in three principal domains: social interaction, language and behavioural inflexibility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental syndromes with the common feature of dysfunctional reciprocal social interaction. In this project we will investigate the role of genes that increase the risk of ASD in the development of behaviours using an animal model. This work will lead to a better unders ....Autism is a developmental neuropsychiatric syndrome characterised by impairments in three principal domains: social interaction, language and behavioural inflexibility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental syndromes with the common feature of dysfunctional reciprocal social interaction. In this project we will investigate the role of genes that increase the risk of ASD in the development of behaviours using an animal model. This work will lead to a better understanding of the genetic basis of ASD.Read moreRead less
Deciphering The Mechanisms For Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$496,321.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less
A Molecular Approach To Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we will examine the effects of specific nerve cell guidance molecules by generating transgenic mice that produce these molecules only in the olfactory system. We can then determine what changes occur to the nerve cells when these extra molecules are produced. The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less
Promoting Plasticity And Functional Recovery In The Adult Brain: Enrichment And Transcranial Magnetic Stimulation
Funder
National Health and Medical Research Council
Funding Amount
$402,493.00
Summary
The adult human brain is unable to repair itself: axons do not regenerate effectively and there is limited reorganisation of remaining projections. Our research directly addresses how to form anatomically accurate and thus functionally useful networks through improving axonal regeneration per se, but more importantly it investigates clinically relevant, non-invasive methods that encourage the remaining nerve cells to reorganise, maximising the surviving resources of the damaged brain.
Characterisation Of Substance P Antagonists As A Novel Therapeutic Intervention For Use In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other cause. The economic and social cost of head injury to the community is enormous with billions of dollars spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have demonstrated that much of the morbidity following TBI is associated with the development of ....Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other cause. The economic and social cost of head injury to the community is enormous with billions of dollars spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have demonstrated that much of the morbidity following TBI is associated with the development of a secondary injury process that occurs between hours to days after the insult. This delayed progression of injury suggests that appropriate pharmacologic intervention can prevent, or at least attenuate, this secondary injury process with a resultant improvement in outcome. Over the past 15 years, a number of groups, including ours, have been investigating the secondary mechanisms associated with the development of functional deficits after TBI. Our previous studies have demonstrated that decline in brain free magnesium is associated with functional deficits after experimental brain injury, and that magnesium administration after injury can improve outcome. Magnesium is now on clinical trial as a pharmacologic intervention. Recent studies have suggested that magnesium decline facilitates neurogenic inflammation, which has been associated with oedema formation, oxidative damage and cell death. Although a number of neuropeptides have been implicated in this process, it is thought that substance P release is closely associated with these pathophysiological processes. Therefore, inhibiting neuropeptide release, or inhibiting substance P binding, may offer a novel therapeutic approach for the attenuation of oedema and development of neurologic deficits after TBI. This proposal will use a combined biochemical, pharmacologic and behavioural approach to characterise the role of neuropeptides in brain trauma, and attempt to develop a novel therapy for use in clinical trauma.Read moreRead less
Long Term Outcome From Early Childhood Brain Injury: 10 Year Follow Up
Funder
National Health and Medical Research Council
Funding Amount
$338,900.00
Summary
The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally he ....The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally held view that children are resilient and recover fully from early brain insult. Rather, we have shown that, up to 5 years post-TBI, many children experience impairments in physical, cognitive and behavioural function. These impairments result in educational, vocational, social and emotional problems, limiting the child's capacity to meet developmental expectations and achieve adequate quality of life. The implication is that these problems will lead to life-long disability, resulting in high levels of individual, family and community burden. However, with follow-up data limited to 5 years, there remains a possibility that ongoing developmental processes may support an extended recovery period in childhood TBI, in comparison to the 2-year period cited in adult models. The review of this sample, 10 years post-injury, provides an unprecedented opportunity to address this possibility and to document recovery-outcome as children move into adolescence and adulthood. Not all children experience problems post-injury. However, predicting individual outcome remains a significant challenge, with particular clinical relevance to treatment and follow-up. Thus, the second aim of the proposed study is to examine factors that contribute to recovery and outcome.Read moreRead less
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
Understanding The Role Of The Olfactory Ensheathing Cell In The Olfactory Sensory System
Funder
National Health and Medical Research Council
Funding Amount
$494,000.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine how one specialized type of cell, the olfactory ensheathing cell, helps the nerve cells to grow and regenerate. Information we obtain about how this system develops and regenerates may be useful in treating brai ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine how one specialized type of cell, the olfactory ensheathing cell, helps the nerve cells to grow and regenerate. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we will examine how olfactory nerve cells interact with the ensheathing cells. We will use transgenic mice in which the different cells are marked by separate colours which will allow us to easily identify the cells and see where they grow. In addition, we will also examine the behaviour of live cells as they are growing. In the past all attempts to understand how nerve cell connections are formed in the olfactory system have used dead tissue that has been permanently preserved. In this project we have the unique opportunity to visualise living nerve cells to enable us to determine how the cells interact with the ensheathing cells. The advantage of this approach is that it allows us to identify important interactions as they occur, rather than attempting to decipher them after they have occurred. An analogy would be watching a football game live and observing how goals were scored and appreciating the performance of individual players versus trying to guess from the final score how the game was played and who the key performers were. These experiments will provide important information about how the olfactory ensheathing and nerve cells grow and regenerate.Read moreRead less
Development Of A Scorpion Toxin For Tumour Imaging
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
The aim of this project is to develop a tool for visualising tumours during surgery. Surgical removal of tumours remains the foundation of cancer treatment, but the ability to distinguish the margin between cancerous and healthy cells is imprecise. We will explore the potential of a scorpion toxin that selectively targets cancer cells, as a tumour imaging agent. This project has the potential to dramatically enhance patient survival as a result of improving treatments for cancer.