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.
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.
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.
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
Dopamine-2 Receptor Antibody In Movement And Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$415,783.00
Summary
Autoimmune movement and psychiatric disorders are a common cause of neurological disability young adults and adolescents. We have identified a subgroup of patients whose disease is associated with an autoimmune reaction. Our study will identify the earliest immune responses against the brain in children with autoimmune movement and psychiatric disorders. Identifying these early immune responses will allow early and directed treatments to prevent disability and death in the future.
The Australian Parkinson's Project - Uncovering Genetic Risk Factors For Sporadic PD
Funder
National Health and Medical Research Council
Funding Amount
$768,546.00
Summary
Parkinson s disease (PD) is a progressively disabling movement disorder afflicting many elderly Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemicals and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration, but it is believed that complex interactions between inherited (genetic) and environmental factors contribute significantly to the phenomenon. This ....Parkinson s disease (PD) is a progressively disabling movement disorder afflicting many elderly Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemicals and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration, but it is believed that complex interactions between inherited (genetic) and environmental factors contribute significantly to the phenomenon. This project aims to learn more about these complex interactions and their association with PD. People with PD and unaffected individuals will be recruited from throughout Australia and we will look for specific combinations of genetic, environmental and lifestyle factors that either increase or decrease an individual's risk for PD. This research will identify the most common dominant genetic and environmental influences for PD in Australia, enabling scientists to focus on the most relevant biological pathways to target therapeutically.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
Tackling The Complex Pathogenesis Of Non-Alzheimer Dementias And Motor Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$948,684.00
Summary
I research dementia and motor syndromes as there are no mechanistic treatments for these disorders, and for many there are no treatments at all. Without being able to identify the same diseases and differentiate them from other diseases, no treatments will be successful. To develop more reliably detection methods for these diseases, I perform longitudinally studies where the participants agree to donate serial biological samples and their brain tissue at death.
Motor Functioning In Autism And Asperger's Disorder: Furthering Current Neurobehavioural And Clinical Definitions
Funder
National Health and Medical Research Council
Funding Amount
$354,932.00
Summary
While it is well known that autism and Asperger's disorder are associated with social, communicative, and behavioural symptoms, it is less well known that affected individuals also have considerable movement and coordination difficulties. For example, these children often have problems with hand writing, walking, hopping, skipping, catching, and running. These skills are very important for success at school; for example, if children are unable to participate in school sports they often feel isol ....While it is well known that autism and Asperger's disorder are associated with social, communicative, and behavioural symptoms, it is less well known that affected individuals also have considerable movement and coordination difficulties. For example, these children often have problems with hand writing, walking, hopping, skipping, catching, and running. These skills are very important for success at school; for example, if children are unable to participate in school sports they often feel isolated and rejected from the peer group. Also, hand writing problems have a significant impact on children's academic performance. Our previous research has suggested that there may be particular patterns of motor problems that characterise individuals with autism and Asperger's disorder. Our proposed research aims to use the kinds of 3D motion analysis technology used in the movie industry to capture exactly how people affected by these conditions move and respond to the environment. This study will enable us to highlight particular parts of the brain-motor circuitry that are affected by these disorders and will also enable us to more clearly distinguish how autism is different from Asperger's disorder. Ultimately, it is hoped that our motor investigations will lead to improved assessment and interventions for these disorders.Read moreRead less
Advances In The Understanding Of Autoimmune Encephalitides And Associated Movement Disorders In Children
Funder
National Health and Medical Research Council
Funding Amount
$68,832.00
Summary
Encephalitis in childhood can be devastating with long lasting effects and mortality. This research focuses on children who suffer from encephalitis due to an autoimmune process. In such cases many children present with involuntary abnormal body movements. This project will explore whether differences in the nature of these movements or in electroencephalography or brain imaging with MRI, can help early differentiation of different types of autoimmune encephalitis.