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Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertake ....Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertaken. We anticipate that the product will be of major commercial interest. We will further explore what is a rapidly expanding marketplace and ensure we maximize the commercial return on this product.Read moreRead less
Glutathione is a natural antioxidant, which is known to protect cells in the body from chemical damage. A small part of the glutathione in cells is found in the mitochondria, a structure that is involved in producing the chemical energy needed for normal cell function. The mitochondria are also involved under some circumstances in promoting the death of cells. Although glutathione in general has been well studied, much less attention has been paid to the function of glutathione in mitochondria, ....Glutathione is a natural antioxidant, which is known to protect cells in the body from chemical damage. A small part of the glutathione in cells is found in the mitochondria, a structure that is involved in producing the chemical energy needed for normal cell function. The mitochondria are also involved under some circumstances in promoting the death of cells. Although glutathione in general has been well studied, much less attention has been paid to the function of glutathione in mitochondria, particularly in cells from the brain. Our recent studies indicate that this mitochondrial pool of glutathione is particularly important in limiting the death of cells from the brain when exposed to damaging substances that are increased in some diseases. Thus, the capacity of mitochondrial glutathione to deal with such substances might be a factor in determining the extent of cell loss in the brain, which is an important determinant of symptoms in some of the major neurological diseases. Consistent with this possibility, we have obtained evidence indicating that decreases in glutathione in the mitochondria contribute to the cell death and brain damage that results from a stroke. In our proposed studies, we will investigate the function of mitochondrial glutathione in the two major cell populations from the brain, neurons and astrocytes. We will characterise the protective role of the glutathione and investigate how it enters the mitochondria and what factors influence the amount that is present. This will provide new insights into the function of glutathione in the mitochondria and could also suggest novel approaches for manipulating this antioxidant pool. We will also study models of stroke and some related brain disorders to more directly test the role of this antioxidant in disease and to assess whether manipulating the content of glutathione in the mitochondria has the potential to reduce damage and improve function in these disordersRead moreRead less
The Incidence And Genetics Of The Infantile Epileptic Encephalopathies
Funder
National Health and Medical Research Council
Funding Amount
$175,224.00
Summary
Severe epilepsies with frequent seizures and cognitive impairments in the first 18 months of life are known as ‘infantile epileptic encephalopathies’ (IEE). The cause of IEE is unknown in many patients, although presumed genetic. This study of patients with IEE in Victoria aims to describe the incidence of IEE, and understand the genetic causes of IEE. Understanding the causes of IEE will be the first step towards development of urgently-needed novel therapies for these devastating conditions.
Down syndrome (DS) individuals have 3 copies of chromosome 21. I am proposing to do my PhD to investigate the role of a gene existing on chromosome 21 called Intersectin 1. This gene, when over-expressed might be responsible for manifestation of intellectual impairment in Down syndrome. I will be examining the consequence of altered/over-expression of this gene in receptor trafficking, cell signalling and histology of the brain to identify the differences between affected individuals and the nor ....Down syndrome (DS) individuals have 3 copies of chromosome 21. I am proposing to do my PhD to investigate the role of a gene existing on chromosome 21 called Intersectin 1. This gene, when over-expressed might be responsible for manifestation of intellectual impairment in Down syndrome. I will be examining the consequence of altered/over-expression of this gene in receptor trafficking, cell signalling and histology of the brain to identify the differences between affected individuals and the normal population.Read moreRead less
Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.
How The Dosage Of A Down Syndrome Candidate Gene Affects Neural Circuitry And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$414,961.00
Summary
In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.
Pathophysiological Decision-making In Children With Obsessive-compulsive Disorder And Tic Disorders: Action-selection And Imaging Correlates
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Why is it that a person with obsessive-compulsive disorder (OCD) has trouble deciding whether or not to wash their hands? We scanned the brains of teenagers with OCD while they made decisions and found that they had difficulty using cues in their environment to direct choices. This may be an early vulnerability for the development of the disorder that could guide prevention. We plan to check if that difficulty is present in younger children with OCD and their family members.
Mechanism Of Action Of A Quinazolinone In Models Of PD
Funder
National Health and Medical Research Council
Funding Amount
$667,548.00
Summary
By the time symptoms of Parkinson's disease (PD) appear, 60-70% of the cells in a crucial part of the brain called the substantia nigra have been destroyed and within a few years of diagnosis, most of the remaining cells have died. This project investigates the causes of this cell loss and a how a new class of compounds could interrupts the process. Success in achieving the aims of this proposal will add to our knowledge of the causes of neuronal death in PD
Shaken Baby Syndrome: Characterization Of A Model And Evaluation Of Novel Pharmacological Therapies
Funder
National Health and Medical Research Council
Funding Amount
$412,460.00
Summary
Shaken baby syndrome is a form of traumatic brain injury in infants less than 2 years of age. It results in death in 10-40 % of cases, and neurological problems in survivors. No treatment exists largely because there is no well characterized model of the syndrome that replicates the human situation. This study will fully characterize our newly developed model of shaken baby syndrome and examine the effectiveness of a novel interventional strategy targeting brain swelling.
Optimum Thiamine Dose For Treatment And Prevention Of Wernicke-Korsakoff Syndrome (WKS): A Randomised Controlled Trial Targeting Aboriginal People.
Funder
National Health and Medical Research Council
Funding Amount
$1,293,716.00
Summary
Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for eff ....Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for effective treatment of WKS in an Aboriginal setting.Read moreRead less