Detection Of Somatic Mutations In Sporadic Epilepsies
Funder
National Health and Medical Research Council
Funding Amount
$1,256,166.00
Summary
Finding genetic causes of epilepsies is essential for refining treatments and genetic counseling. Genetic mutations may occur after fertilization (somatic mutations). These can be difficult to detect by routine genetic tests. We aim to identify somatic mutations by: very deep sequencing of blood to find low concentrations of mutations, analysing DNA from the cerebrospinal fluid, and analysing DNA obtained from the back of the nose which is closely related to brain tissue.
Epilepsy is the name of a group of disorders where seizures occur. 5% of people will have at least one seizure. Seizures accompanied by fever (febrile) are common in early childhood. Most forms of epilepsy and febrile seizures have an inherited component. Progress in finding genes for common forms of epilepsy has been slow, probably because they are due to the interaction of a number of genes. Four genes for rare epilepsies with single gene inheritance have been identified. These genes code for ....Epilepsy is the name of a group of disorders where seizures occur. 5% of people will have at least one seizure. Seizures accompanied by fever (febrile) are common in early childhood. Most forms of epilepsy and febrile seizures have an inherited component. Progress in finding genes for common forms of epilepsy has been slow, probably because they are due to the interaction of a number of genes. Four genes for rare epilepsies with single gene inheritance have been identified. These genes code for subunits of ion channels in cells. We study families where many individuals have seizures and carefully diagnose the seizures types. This work has resulted in the description of 5 new inherited epilepsies and led to discovery of 3 of the 4 known genes. The most important new inherited epilepsy is Generalized Epilepsy with Febrile Seizures Plus (GEFS+). GEFS+ accounts for many children with febrile seizures restricted to early childhood, or where seizures continue into mid-childhood. GEFS+ families may contain an individual with severe generalized epilepsy with intellectual disability. In a Tasmanian family with GEFS+, we found a gene defect in the sodium channel of nerve cells in the brain. We plan to study more families with GEFS+. We believe that specific severe childhood epilepsies may occur in families with GEFS+. If so, then the underlying cause of these serious disorders may be gene defects of GEFS+. Finding such genes will help to understand the basis of seizures and ultimately lead to targeted therapies. The second major focus of our work on GEFS+ is to use family studies to understand how different types of seizures are inherited, and to gain insights into the gene interactions underlying common epilepsies. We plan to study isolated cases of GEFS+ for the gene defects found in families. This strategy will reveal whether the same genes are important in the genetics of the common epilepsies.Read moreRead less
Targeting NPY Mechanisms In Rodent Models Of Generalised Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$437,637.00
Summary
This project will provide important information regarding the pharmacological mechanisms by which NPY acts to suppress seizures in animal models of epilepsy. It will provide strategies regarding potential new treatments of absence epilepsy.
A Study Of The Impact Of Treating Electrographic Seizures In Term Or Near-term Infants With Neonatal Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$1,365,184.00
Summary
Seizures in the newborn infant are common and may be harmful to the developing brain. They are not always recognised. This study investigates whether or not treating all seizures detected using a bedside brain activity monitor improves developmental outcome, compared to just treating seizures that doctors recognise.
NPY Suppresses Seizures And Modulates Thalamocortical Activity In Animal Models Of Generalized Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$386,020.00
Summary
Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled ....Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled with current medications. Recently there has been considerable interest in the role that chemical in the brain, such as neuropeptide Y (NPY), may play in epilepsy. The research proposed will examine the role of NPY in several animal models of absence epilepsy. We have recently shown that NPY suppresses absence seizures in a rat genetic model of generalised epilepsy, and that this appears to be mediated by Y2 receptors. This work will build on these novel findings, and determine the localisation of the effect within the brain, and the underlying mechanism. We will check NPY effects across several models in different species, a genetic rat model with spontaneous seizures, and in mice treated with a chemical to induce seizures. This will determine its broad applicability. We will also determine the effects of removal of NPY or NPY receptors on the effects of NPY on seizure expression. Finally, brain recording techniques will be applied to determine the mechanism and site within the brain underlying the protective actions of NPY. The project has the potential to provide novel insights into the role of NPY in the expression and modulation of absence seizures. NPY related mechanisms might represent targets for the development of a new class of therapeutic agents for the treatment of absence epilepsy. Targets that are identified as being important in the expression of absence seizures may also prove to be relevant in other types of generalised epilepsy syndromes.Read moreRead less
Mechanisms Underlying Generation Of Febrile Seizures In Mouse Models Of Human Familial Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$304,559.00
Summary
Febrile Seizures (FS) affect 3% of children aged 0.5 - 6 yrs and have been proposed as an indicator of severe forms of adult generalized epilepsy. Mechanisms underlying FS generation are unknown although studies of Australian families suffering from epilepsy have linked 2 genes to FS. We have generated mice expressing these 2 genes. Aims and Outcomes: to investigate events triggering FS which will provide important insights into why FS occurs in children. (NB: CIA 2 yr career interruption)
Young women negotiating from the margins of education and work: towards gender justice in educational and youth policies and programs. Young women who leave school early are the most economically disadvantaged young people in the labour market. We will investigate the educational, labour market, biographical and social experiences of these young women, and their inter-actions with teachers and youth service providers. We will identify trends, differences and similarities across rural and urban l ....Young women negotiating from the margins of education and work: towards gender justice in educational and youth policies and programs. Young women who leave school early are the most economically disadvantaged young people in the labour market. We will investigate the educational, labour market, biographical and social experiences of these young women, and their inter-actions with teachers and youth service providers. We will identify trends, differences and similarities across rural and urban locations and across generations, and develop a profile of factors and programs most likely to help these young women negotiate their post-school lives. The research findings will enrich gender justice and social theory and contribute to policy and program development in the education and youth services sectors.
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LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS
Funder
National Health and Medical Research Council
Funding Amount
$461,250.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.Read moreRead less
Supply, Demand And The Distribution Of Health Services In Australia
Funder
National Health and Medical Research Council
Funding Amount
$308,038.00
Summary
The distribution of medical services and its impact on access and equity is widely recognised as a key concern of the Australian community. Access and equity are key indicators to the public of the performance of a health system. These concerns have led to the adoption of major policy goals under Medicare relating to equitable access to medical services for the population as a whole. Furthermore, both the community and policy makers have expressed high levels of concern over the distribution of ....The distribution of medical services and its impact on access and equity is widely recognised as a key concern of the Australian community. Access and equity are key indicators to the public of the performance of a health system. These concerns have led to the adoption of major policy goals under Medicare relating to equitable access to medical services for the population as a whole. Furthermore, both the community and policy makers have expressed high levels of concern over the distribution of medical services between sub-markets and sub-populations, in particular, in the distribution of medical services between urban and rural-remote areas. This project, for the first time, comprehensively examines the performance of Medicare in terms of access to medical services over time. Australian data sets, largely untapped by economic modelling, will be used for analysis of the relationships between the distribution of, access to, and demand and fees for Australian medical services and their impact upon mortality over time. The study will result in the first comprehensive Australian description of access and supply of different medical services by social group and by geographic location over time. Furthermore it will provide evidence on the key determinants of distribution and changes in the distribution of medical services and estimates the likely effects of policy instruments designed to address the distribution of, and access to, medical services.Read moreRead less
Reinventing Philosophy as a Way of Life. The core aim of this project is to examine modern re-inventions of the classical ideal of philosophy as a way of life. It will investigate the reanimation of this idea in post-Kantian philosophy, including well-known figures such as Nietzsche but also neglected figures such as Jean-Marie Guyau. The research will be highly significant in providing the first sustained study of how 19th and 20th century European philosophy transformed ancient philosophical s ....Reinventing Philosophy as a Way of Life. The core aim of this project is to examine modern re-inventions of the classical ideal of philosophy as a way of life. It will investigate the reanimation of this idea in post-Kantian philosophy, including well-known figures such as Nietzsche but also neglected figures such as Jean-Marie Guyau. The research will be highly significant in providing the first sustained study of how 19th and 20th century European philosophy transformed ancient philosophical schools, such as Epicureanism and Stoicism. Read moreRead less