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Identification And Characterisation Of Novel Mouse Models For Recessively Inherited Deafness.
Funder
National Health and Medical Research Council
Funding Amount
$504,750.00
Summary
Hearing loss affects 10% of Australians. Approximately 1 in 1000 children is born deaf. Another 1 in 1000 people develops hearing loss by adulthood. A progressive hearing impairment occurs with age so that more than 50% of people over the age of 75 have a substantial hearing loss. The financial, social and personal costs of deafness are significant. Deafness is caused by environmental and- or inherited factors. Environmental risk factors include premature birth, infections and exposure to loud n ....Hearing loss affects 10% of Australians. Approximately 1 in 1000 children is born deaf. Another 1 in 1000 people develops hearing loss by adulthood. A progressive hearing impairment occurs with age so that more than 50% of people over the age of 75 have a substantial hearing loss. The financial, social and personal costs of deafness are significant. Deafness is caused by environmental and- or inherited factors. Environmental risk factors include premature birth, infections and exposure to loud noise. Inherited factors include changes (mutations) in one of many genes whose products are essential for normal hearing. In the majority of children and young people with a hearing impairment the underlying cause is genetic. It is also thought that genetic predisposition frequently contributes to the early onset and the severity of age-related hearing loss. However, it has been difficult to identify the genes causing deafness, and as a consequence we know relatively little about what these genes do. The mouse ear is very similar to the human ear and in this application we propose to use mice to identify and study deafness genes. Australia has a unique resource of mice that are being especially bred to uncover genetic diseases. We have shown that 1 in a 1,000 of these mice have a genetic hearing loss similar to that found in most newborns and young people. These mice therefore provide us with an exceptional opportunity to discover novel deafness genes, which again will provide us with more information about how we hear. We will investigate why changes in these genes causes hearing loss and this information will allow us to determine in detail how genetic and environmental factors lead to hearing loss in young and old. The results will immediately allow us to offer earlier diagnosis and better counselling to affected families, and in the longer term we believe our research will enable us to develop improved or novel treatments to delay or prevent deafness.Read moreRead less
Identification And Characterisation Of Mouse Models For Recessively Inherited Deafness.
Funder
National Health and Medical Research Council
Funding Amount
$691,893.00
Summary
Hearing loss affects 10% of Australians. Approximately 1 in 1000 children are born deaf. A progressive hearing impairment occurs with age so that more than 50% of people over the age of 75 have a substantial hearing loss. The financial, social and personal costs of deafness are significant. Deafness is caused by environmental and-or inherited factors. In the majority of children and young people with a hearing impairment the underlying cause is genetic. It is also known that genetic predispositi ....Hearing loss affects 10% of Australians. Approximately 1 in 1000 children are born deaf. A progressive hearing impairment occurs with age so that more than 50% of people over the age of 75 have a substantial hearing loss. The financial, social and personal costs of deafness are significant. Deafness is caused by environmental and-or inherited factors. In the majority of children and young people with a hearing impairment the underlying cause is genetic. It is also known that genetic predisposition frequently contributes to the time of onset and the severity of age-related hearing loss, as well as susceptibility to noise and ototoxic drugs. It has proven difficult to identify the genes causing deafness, especially those genes associated with age-related hearing loss and susceptibility to noise and ototoxic drugs. The mouse ear is very similar to the human ear and therefore well suited to genetic and molecular studies of human deafness. Australia has a unique resource of mutagenised mice that are being bred to uncover recessive deafness, the most common type of inherited hearing loss. We have so far identified 10 mouse strains with recessive hearing impairment. 5 of the strains have an age-related hearing loss. We have identified the genetic mutation in 3 of the strains, including a mutation in a novel deafness gene. Another strain has a mutation in a novel deafness gene yet to be identified. We propose to continue the studies of these and additional mice. We will investigate why changes in these genes cause hearing loss and determine in detail how genetic and environmental factors lead to hearing loss in young and old. The results will allow us to offer earlier diagnosis and better counselling to affected families, and in the longer term we believe our research will enable us to develop improved or novel treatments to delay or prevent deafness.Read moreRead less
Inflammation-associated S100 Proteins: Links Between Arthritis And Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$454,691.00
Summary
Deeper understanding of the basic contributions of inflammation to cardiovascular disease can lead to better strategies for treatment and diagnosis. There are shared mechanisms in rheumatoid arthritis and these patients are at significantly higher risk of myocardial infarction and heart failure than the healthy normal population. This project will improve heart health because it will address how newly-recognised proteins, called S100 proteins, mediate pathogenesis and how they are regulated in c ....Deeper understanding of the basic contributions of inflammation to cardiovascular disease can lead to better strategies for treatment and diagnosis. There are shared mechanisms in rheumatoid arthritis and these patients are at significantly higher risk of myocardial infarction and heart failure than the healthy normal population. This project will improve heart health because it will address how newly-recognised proteins, called S100 proteins, mediate pathogenesis and how they are regulated in cells by various therapeutic drugs. We developed a potential diagnostic test that distinguishes patients with angina from those with arthritis and this could be useful in improving diagnosis and following treatment of patients with cardiovascular disease or arthritis. We find that some anti-inflammatory drugs enhance S100 gene expression whereas our preliminary data indicates that some cholesterol-lowering drugs (statins) reduce it. Results of treating patients with arthritis with statins will add to understanding of why cholesterol-lowering drugs commonly used in management of CVD patients may be effective in treating symptoms in arthritis sufferers and could contribute to changes in clinical management of these patients.Read moreRead less
Hydatid disease is caused by a parasitic infection that is transmitted to people by animals. The disease causes substantial human morbidity and mortality worldwide, and is endemic in Australia. Currently available drugs are poorly effective against the parasite and treatment of the disease relies mainly on surgical removal of often large parasitic cysts, where this is possible. Blood tests to identify people who are infected rely on the use of parasite samples obtained from animals, which leads ....Hydatid disease is caused by a parasitic infection that is transmitted to people by animals. The disease causes substantial human morbidity and mortality worldwide, and is endemic in Australia. Currently available drugs are poorly effective against the parasite and treatment of the disease relies mainly on surgical removal of often large parasitic cysts, where this is possible. Blood tests to identify people who are infected rely on the use of parasite samples obtained from animals, which leads to difficulties with adequate supply of material and quality control. Research in this laboratory discovered that the hydatid parasite produces a protein that binds the drug cyclosporin A and that specific antibodies are made to this protein in hydatid patients. Preliminary research by others found that cyclosporin A had anti-parasitic effects on hydatid disease in an animal model system. This research project will examine in detail the characteristics of the cyclophilin protein and related proteins, in the hydatid parasite, their interaction with cyclosporin A, the effects of cyclosporin A on the parasite in defined culture conditions, the mechanism by which cyclosporin A exerts anti-parasitic effects and the prospects for use of cyclophilin in tests for the diagnosis of human hydatid disease. The research will contribute to a better understanding of the basic biology of this pathogen and may identify improved methods for the chemotherapy and diagnosis of infection.Read moreRead less
SNAC2: A Randomised Trial Of Extending Sentinel Node Based Management To Women With Larger Or Multifocal Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,266,430.00
Summary
SNAC2 extends the work begun in SNAC1, which recruited 1,088 women over 4 years. SNAC1 will determine if sentinel node biopsy causes less arm problems than axillary clearance. The goal of SNAC2 is to establish the risk of local recurrence and long term safety of sentinel node biopsy, especially for women with larger or multiple tumours. SNAC2 is needed to determine whether the smaller operation gives cure rates as good as axillary clearance. If it does, then it will become standard practice.
Massively Parallel Sequencing And PCR Optimised For DNA-based Diagnostics And Discovery
Funder
National Health and Medical Research Council
Funding Amount
$201,664.00
Summary
The next generation of medical diagnostics and discovery in disease research will involve the marriage of PCR, a tool used to amplify large amounts of DNA from small starting quantities, and �next generation� sequencing, a way to sequence lots and lots of DNA on a single instrument run. This study aims to describe methods which allow scientists to screen hundreds of disease genes in hundreds of people simultaneously with high accuracy and high efficiency.
The Diagnosis Of Obstructive Sleep Apnea In Primary Care
Funder
National Health and Medical Research Council
Funding Amount
$295,075.00
Summary
The gold standard method for diagnosis of sleep apnea is the overnight sleep study. These tests are expensive, have long waiting lists and are hard to access outside larger cities. We aim to determine if general practitioners can combine information from questionnaires and a simple home diagnostic test, to confirm or rule out sleep apnea. The results of this study will eventually lead to more accessible and efficient diagnosis and treatment of this common condition.
Developing A Skin Test For Early Diagnosis Of Alzheimer's Disease And For Monitoring Effectiveness Of Treatment
Funder
National Health and Medical Research Council
Funding Amount
$285,000.00
Summary
Approximately 140,000 Australians suffer from Alzheimer's disease (AD). As the ageing population continues to grow, this number will double by the middle of the next century unless a cure or prevention is found. Scientists are continuously seeking new, more effective diagnostic tests in an effort to make it easier to diagnose AD in its early stages. Being able to recognize symptoms early and obtain an accurate diagnosis would give affected individuals a greater chance of benefiting from putative ....Approximately 140,000 Australians suffer from Alzheimer's disease (AD). As the ageing population continues to grow, this number will double by the middle of the next century unless a cure or prevention is found. Scientists are continuously seeking new, more effective diagnostic tests in an effort to make it easier to diagnose AD in its early stages. Being able to recognize symptoms early and obtain an accurate diagnosis would give affected individuals a greater chance of benefiting from putative treatments. However, there is no single, comprehensive diagnostic test for AD. Diagnostic tests (including peripheral markers) that can help to reliably diagnose AD at an early stage are needed as are tests that can help in monitoring the progression of AD, including response to therapy. The accuracy and clinical utility of previously proposed peripheral markers (platelets and pupil dilation test) is questionable. The only way to confirm a diagnosis of AD is through autopsy. We have obtained a provisional patent application for the use of a skin test for early diagnosis of AD (Patent No: PQ2881-99). This test is based on our extensive research over the past decade to understand the biochemical mechanisms underlying the txic vascular actions of beta amyloid protein. This protein has been implicated in the pathology of AD and it accumulates in the brain, peripheral tissues and is present in circulating blood of AD patients. The test is based on our discovery that vascular effects of Ab could be detected in the peripheral microcirculation .We now wish to further examine the utility of this novel skin test. If the test is sensitive, it could be used for screening; if it is specific it would be useful for confirmation of suspected AD. If the test is sensitive to change in clinical status it would help select treatments that might cure or improve the symptoms of AD.Read moreRead less
Mechanisms Of Pharyngeal Collapse In Obstructive Sleep Apnoea Defined By Optical Coherence Tomography
Funder
National Health and Medical Research Council
Funding Amount
$476,764.00
Summary
Obstructive sleep apnoea is characterised by intermittent collapse of the upper airway (throat) resulting in episodes of decreased blood oxygen levels, increased blood pressure and sleep disruption. Obstructive sleep apnoea is common, affecting 5% of middle-aged adults, and is associated with worsening health, increased motor vehicle accidents and increased risk of heart disease. However the mechanisms responsible for obstructive sleep apnoea are not well understood. One reason for this lack of ....Obstructive sleep apnoea is characterised by intermittent collapse of the upper airway (throat) resulting in episodes of decreased blood oxygen levels, increased blood pressure and sleep disruption. Obstructive sleep apnoea is common, affecting 5% of middle-aged adults, and is associated with worsening health, increased motor vehicle accidents and increased risk of heart disease. However the mechanisms responsible for obstructive sleep apnoea are not well understood. One reason for this lack of understanding is that current diagnostic techniques can not accurately measure changes in the size and shape of the upper airway during sleep. Such information is vital for the accurate diagnosis and treatment of obstructive sleep apnoea. This project proposes to use a technique called endoscopic optical coherence tomography (eOCT), recently developed by ourselves, to measure the changes in upper airway size and shape in patients with obstructive sleep apnoea during wakefulness and, importantly, during sleep. A prototype of the system has been developed. Preliminary in vivo studies have been performed in the human upper airway and the results from these preliminary trials have been published. To our knowledge, world-wide, this is the only such system capable of making these measurements. The studies proposed in this application will provide a better understanding of the mechanisms underlying obstructive sleep apnoea and may lead to the development of greatly improved and more specific treatments that are tailored to the exact needs of the individual patient.Read moreRead less