Endocrine Therapy Tolerance As A Cancer Cell Survival Mechanism For Late Recurring Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$450,083.00
Summary
~25% of breast cancer deaths are attributable to cancers that have failed endocrine therapy and recur >5 years after primary diagnosis. These cancers are not well understood because their long latency makes them difficult to study. We have new models of this disease that identify a “therapy tolerant” population, and this is likely to re-emerge to cause late recurrence. Our work could potentially identify new biological tests and therapeutic strategies to treat late recurring breast cancer.
Double Stranded RNA - The Common Pathogenic Agent In Expanded Repeat Genetically Inherited Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
At least twenty human genetic diseases are due to the expansion of existing repeat sequences beyond a common threshold copy number. While many of these diseases have a common mutation mechanism and share many clinical features the molecular steps critical to their pathogenesis are not yet understood. This project will test the hypothesis that expanded repeat containing RNA, specifically in its double-stranded form, is a common pathogenic agent in many of these diseases.
First Generation Mouse Models Of MtDNA Disease: Testing Genotype/phenotype Predictions
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Mitochondrial diseases comprise a diverse group of inherited diseases affecting infants, children and adults. These disorders result from defective energy production by the mitochondria, tiny structures in all cells which have their own unique DNA. This mitochondrial DNA is inherited only from our mothers. To make energy for cells to function normally, special enzymes are produced in the mitochondria from mitochondrial and nuclear genes. In their most severe form mitochondrial disease results in ....Mitochondrial diseases comprise a diverse group of inherited diseases affecting infants, children and adults. These disorders result from defective energy production by the mitochondria, tiny structures in all cells which have their own unique DNA. This mitochondrial DNA is inherited only from our mothers. To make energy for cells to function normally, special enzymes are produced in the mitochondria from mitochondrial and nuclear genes. In their most severe form mitochondrial disease results in infants with muti-system failure. Adult forms are less severe, with symptoms including epilepsy, cardiomyopathy, late-onset blindness or deafness, and commonly diabetes. We do not understand why different mitochondrial mutations result in such diverse symptoms, and no therapies have been consistently successful. Unusual features of mitochondrial DNA has meant that it has remained beyond the reach of techniques which are commonly used now to produce mice with altered genes. These so-called 'mouse models' are powerful tools to better understand human diseases and importantly, to enable experimental therapies to be tested and improved. This grant proposes a novel method of producing such mouse models, for the first time allowing mice with different levels of defective mitochondrial function to be produced to model the human diseases. In the proposed work, mitochondria from different mouse species will be introduced into laboratory mice. This unusual approach is based on previous work by the investigators who have shown that this produces defective mitochondria in cultured mouse cells. These mice will be allowed to age and the function of mitochondria from different organs tested as the animals age. Secondly, a range of mitochondrial DNA mutations will be produced in cultured cells and mutants selected to make other mice which should accurately model the diverse human diseases.Read moreRead less
The Use Of Probiotics To Reduce The Incidence Of Sepsis In Premature Infants.
Funder
National Health and Medical Research Council
Funding Amount
$808,733.00
Summary
Currently, premature infants are born without the normal immune defenses of infants born at the correct time because the protective factors that normally pass from the mother to the baby during the last few months of pregnancy have not had time to do so. In addition the tiny premature infants are at risk because they need the expertise of intensive care and are therefore separated from their parents and their parents' organisms which healthy term infants normally pick up from the birth canal and ....Currently, premature infants are born without the normal immune defenses of infants born at the correct time because the protective factors that normally pass from the mother to the baby during the last few months of pregnancy have not had time to do so. In addition the tiny premature infants are at risk because they need the expertise of intensive care and are therefore separated from their parents and their parents' organisms which healthy term infants normally pick up from the birth canal and their parents skin. The infants commonly develop infections from organisms living on their skin surfaces or inside their lungs, stomach or bowels. The babies are living in a hospital environment which they need to survive, but they may pick up particularly unhealthy organisms (pathogens) that produce toxins, which are difficult to treat even with antibiotics. These infections are so severe that one-fifth of the babies die, even in Australia where facilities for premature infants are excellent. Two recent studies overseas have shown that giving premature babies special preparations of certain probiotic organisms decreases the chance of babie developing infections. Probiotics are organisms that have health benefits. Probiotics tighten the spaces between cells to stop bacteria getting into the body, produce substances that kill other bacteria and promote the production of immunoglobulin A by the baby's own cells. Immunoglobulin A is a substance that lines the bowel wall and protects the baby from invasion by bacteria. This study will offer this probiotic product to very premature babies in a trial to see if it produces additional benefits for our babies in Victoria. Around five hundred babies will be given the product and five hundred will be given the placebo ( a harmless inert product which will look just like the real probiotic). Currently 23% of our babies get the serious infections and this study is powerful enough to see if we can reduce the number by one third.Read moreRead less
A NESTED CASE CONTROL STUDY EVALUATING THE ASSOCIATION BETWEEN THE FACTOR V LEIDEN GENOTYPE AND ADVERSE PREGANCY OUTCOME
Funder
National Health and Medical Research Council
Funding Amount
$165,990.00
Summary
The factor V Leiden gene mutation is present in 1 in 20 of the general population. Recent studies suggest an association between the factor V Leiden gene mutation and adverse pregnancy outcomes. It is currently recommended that women with a history of recurrent pregnancy loss, including a second or third trimester intrauterine death should be screened for the factor V Leiden mutation. Controlled trials are currently underway assessing efficacy of treatment with anticoagulaton therapy for women w ....The factor V Leiden gene mutation is present in 1 in 20 of the general population. Recent studies suggest an association between the factor V Leiden gene mutation and adverse pregnancy outcomes. It is currently recommended that women with a history of recurrent pregnancy loss, including a second or third trimester intrauterine death should be screened for the factor V Leiden mutation. Controlled trials are currently underway assessing efficacy of treatment with anticoagulaton therapy for women who screen positive. However, population screening is currently not recommended because we do not know the significance of a factor V leiden gene mutation for women without a previous history of adverse pregnancy outcome. The question of why some women with a factor V Leiden mutation experience recurrent pregnancy loss whereas other women do not remains unanswered. The primary aim of this study is to determine whether the maternal and- or fetal genotype for factor V Leiden influences the risk of first and second trimester miscarriage within a cohort of 25,000 pregnant women. The aim of further research in this area is to identify a subset of women at increased risk of a second or third trimester fetal loss, based on a combination of genetic, acquired and environmental thrombophilic risk factors, who may benefit from prophylactic treatment with anticoagulation therapy.Read moreRead less
Enabling Personalised Risk Assessment For Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Bowel cancer screening will be most effective in disease prevention if it is applied proportionately to individual person's risk. Risk-based screening requires a risk calculator to assess personal risk. By utilising existing large, international datasets, I will identify the risk factors specific for different bowel cancer types and incorporate them to upgrade the prediction model that I have developed. This will achieve more accurate risk prediction to enable personalised risk-based screening.
Hyper-sensitivity Of The Circadian System To Light In Delayed Sleep Phase Disorder
Funder
National Health and Medical Research Council
Funding Amount
$378,858.00
Summary
Delayed Sleep Phase Disorder (DSPD) is a circadian rhythm sleep disorder characterized by a difficulty in initiating sleep at night and difficulty in waking at times required for work or school. It is associated with excessive daytime sleepiness, reduced academic and work performance, increased anxiety and depression and reduced quality of life. This study examines increased sensitivity of the brain's 24-hour biological clock to light as a cause of the abnormal timing of sleep in DSPD.