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
Mechanisms Of Mechanotransduction In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have ....Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.Read moreRead less
INVESTIGATING THE VALIDITY OF PRENATAL INSULTS AS RISK FACTORS FOR SCHIZOPHRENIA.
Funder
National Health and Medical Research Council
Funding Amount
$201,100.00
Summary
Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical ma ....Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical make up of the brain and gives rise to long-lasting structural and neurochemical changes in adolescent animals, which resemble changes found in the brains of patients with schizophrenia. We will also assess whether behavioural responses of compromised animals are altered in tests that parallel disturbances seen in patients with schizophrenia. Such abnormal brain development could create an underlying vulnerability in the brain, predisposing individuals with risk factors such as genetic inheritance to develop the symptoms of schizophrenia in later life perhaps only after the complete formation of nerve pathways involved in higher brain functioning. If guinea pigs that have been subjected to low oxygen levels during pregnancy show sustained changes in the structure and neurochemistry in regions of the brain that are altered in patients with schizophrenia it would suggest that these long lasting disturbances could result from problems during pregnancy. Thus, this would support the idea that abnormal brain development during pregnancy is one of the underlying causes of schizophrenia.Read moreRead less
Identifying Neuroanatomical Sub-phenotypes Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$60,129.00
Summary
The clinical presentation of schizophrenia is varied across individuals, and has arguably hindered efforts to determine its cause/s. This project seeks to address this issue by investigating biological commonality in patients, to identify subgroups of schizophrenia patients with similar brain abnormalities, with the overall aim to examine cognitive and clinical characteristics and candidate genetic markers in association with biologically derived subtypes of schizophrenia.
Development And Epilepsy - Strategies For Innovative Research To Improve Diagnosis, Prevention And Treatment In Children With Difficult To Treat Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$456,083.00
Summary
By deciphering pathophysiological mechanisms in epileptogenic developmental disorders and developing mechanism-related, and advanced therapeutic strategies, we expect to discover novel genes and related molecular pathways that are involved in epilepsy and similar disorders. DESIRE will also help preventing the development of the disease after potentially epileptogenic brain insults.
Neurobiology Of Childhood Speech Disorders: Improving Detection, Diagnosis And Clinical Care
Funder
National Health and Medical Research Council
Funding Amount
$994,575.00
Summary
One in 20 children have a speech disorder at school entry, with lifelong deficits in psychosocial, academic and employment outcomes. Little is known about the aetiology of speech disorders, preventing targeted care. We combine expertise in speech pathology, gene discovery and brain imaging, to advance knowledge on gene and brain contributions to speech disorder. We will have direct impacts on clinical care including detection, diagnosis and counselling, optimising outcomes for affected children.
Reducing Morbidities In Preterm Growth Restricted Neonates.
Funder
National Health and Medical Research Council
Funding Amount
$687,214.00
Summary
Intrauterine growth restriction (IUGR) is a serious complication of pregnancy and occurs when fetal growth is abnormal, resulting in a fetus that is smaller than it should be for its given gestational age. IUGR babies are at much greater risk of many short and long-term adverse outcomes. This study investigates the role that adverse cardiovascular development plays in the progression of lung, heart and brain disease in preterm IUGR newborns.
Tuberous Sclerosis And Epilepsy: Using Resected Tissue To Understand Pathogenesis And Inform Management
Funder
National Health and Medical Research Council
Funding Amount
$339,261.00
Summary
Epilepsy is the commonest neurological disorder in childhood and seizures cannot be fully controlled by medications in 30%, often leading to developmental consequences. A major cause of drug-resistant epilepsy is a malformation of the brain’s surface. Surgery is sometimes used to remove these lesions to treat the epilepsy. We will study this tissue to understand its architecture, genetic basis and how it causes seizures. Our results will guide treatment including the best surgical approach.
A Phase I Study Of The First In Class Dual IMiD/bromodomain Inhibitor N-methyl-2-pyrrolidone (NMP) In Relapsed And Refractory Multiple Myeloma.
Funder
National Health and Medical Research Council
Funding Amount
$551,061.00
Summary
We have newly discovered that a simple molecule called NMP has the ability to control myeloma cells that have become resistant to other available treatments. NMP works by enhancing immune function and by killing myeloma cells directly by inhibiting survival signals. NMP is different from all other types of available myeloma treatments. We intend to test the safety and power of NMP in the treatment of myeloma by running a clinical trial of NMP in patients with relapsed myeloma.