Exploiting Sexual Differences In Germline Biology To Resolve The Causes Of Germline Mutation
Funder
National Health and Medical Research Council
Funding Amount
$315,914.00
Summary
Mutagenesis during the production of sex cells is a fundamental biological process and the cause of inherited human disorders. These disorders span the entire spectrum of diseases that have a genetic component, such as autoimmune diseases and cancers, therefore influencing all age groups. A better understanding of the mechanisms underlying this process is a priority since it is the essential knowledge required for understanding all of the factors that contribute to this array of debilitating dis ....Mutagenesis during the production of sex cells is a fundamental biological process and the cause of inherited human disorders. These disorders span the entire spectrum of diseases that have a genetic component, such as autoimmune diseases and cancers, therefore influencing all age groups. A better understanding of the mechanisms underlying this process is a priority since it is the essential knowledge required for understanding all of the factors that contribute to this array of debilitating diseases, and for devising effective preventative and diagnostic measures. To attain this understanding necessitates establishing the mechanistic origins of germline mutagenesis. Two basic approaches are employed to understand this process. The first assesses the incidence of mutation in pedigrees. This identifies the spectrum of risk mutations underlying the specific disease surveyed. Because other biological processes also influence these observations, the results from this approach do not reflect the underlying germline mutation spectra and are therefore not translatable between diseases. As mutations are rare events, it is prohibitive to obtain sufficient observations to resolve the underlying mechanisms. The second approach employs comparative genomic data, and uses differences in germline biology to estimate sex-biased effects. This comparative approach benefits from the accumulation of mutations over vast periods of time. The approach has not, however, been applied to diagnose the mechanistic origins of mutations. In this project, we will apply the enormous volume of comparative sequencing data to relate components of the mutagenic spectrum with sexual differences in germline biology. The project will differentiate between different types of mutations, and their association with specific processes will be established. The results will be a determination of the relative contributions of different mechanisms of mutation to germline mutagenesis.Read moreRead less
PArkin Co-Regulated Gene (PACRG), Parkin And Parkinsonism.
Funder
National Health and Medical Research Council
Funding Amount
$397,740.00
Summary
Parkinson's disease (PD) is a common neurodegenerative disorder affecting greater than two percent of individuals over the age of 65. The disease is characterised by tremor, slowness of movement, rigidity and postural instability. Current treatment regimes may provide some measure of symptomatic relief, but currently there is no treatment to halt or slow the progression of this debilitating disease. PD currently affects an estimated 35,000 people in Australia and this figure is predicted to incr ....Parkinson's disease (PD) is a common neurodegenerative disorder affecting greater than two percent of individuals over the age of 65. The disease is characterised by tremor, slowness of movement, rigidity and postural instability. Current treatment regimes may provide some measure of symptomatic relief, but currently there is no treatment to halt or slow the progression of this debilitating disease. PD currently affects an estimated 35,000 people in Australia and this figure is predicted to increase significantly as the population ages. PD is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years several genes have been identified that can cause PD when disrupted. We have identified a new gene that we believe may be involved in PD. The overall aim of this proposal is to characterise this gene and what role it plays in the development of PD. Understanding the expression and function of this gene may significantly advance our understanding of this disorder. Using these results, we aim to model Parkinson's disease in cellular and animal systems; these may provide powerful insight into the molecular pathway(s) perturbed in PD and a means to develop novel therapeutic approaches to alleviate or prevent the disorder.Read moreRead less
Low Dose Aspirin And Age-related Macular Degeneration: Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,043,189.00
Summary
Age-related macular degeneration (AMD) is a major cause of visual impairment in advanced countries, responsible for nearly half of all legal blindness in Australia. Due to increased life expectancy, the number of people with this progressive late onset disease will double by 2025. Aspirin could prevent or delay the onset of AMD in older persons but its bleeding risk also needs to be considered. This project will determine whether treatment with low dose aspirin reduces incidence or progression o ....Age-related macular degeneration (AMD) is a major cause of visual impairment in advanced countries, responsible for nearly half of all legal blindness in Australia. Due to increased life expectancy, the number of people with this progressive late onset disease will double by 2025. Aspirin could prevent or delay the onset of AMD in older persons but its bleeding risk also needs to be considered. This project will determine whether treatment with low dose aspirin reduces incidence or progression of AMD.Read moreRead less
Genetic Analysis Of The Relationship Between Parental Age And Risk Of Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$301,012.00
Summary
Age-related de novo mutations are widely assumed to explain the association between advanced paternal age and risk of psychiatric illness, but this mechanism cannot explain the known risk to offspring of teenaged parents. We will investigate an alternative hypothesis for risk to children due to parental age, which is that elevated liability to mental illness, arising from shared genetic factors between parents and offspring, leads to delayed, or conversely teenage, parenthood.
Understanding The Etiology Of Psychiatric Disorders Through Whole Genome Analyses
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Psychiatric disorders exert a huge social and economic burden on society. In recent years, large genetic studies have led to important new insights into these disorders. Major new human genomics resources will soon become available. My research will take advantage of these datasets to investigate the genetic basis of key epidemiological features of psychiatric disorders, including risk due to parental age and sex-biased prevalence, and to identify novel risk genes for schizophrenia and autism.
Do NK Cells Limit The Long Term Burden Of CMV In Older Australians And Transplant Recipients?
Funder
National Health and Medical Research Council
Funding Amount
$413,864.00
Summary
Most people are infected with cytomegalovirus at an early age. The virus is not naturally cleared from the body but becomes latent and may be reactivated by stress or inflammation. Repeated immune responses to these reactivations causes more inflammation and wears out the immune system resulting in diseases of aging (eg: cardiovascular disease). Here we investigate which aspects of the immune system can control CMV in healthy people and in renal transplant recipients. We focus on a population of ....Most people are infected with cytomegalovirus at an early age. The virus is not naturally cleared from the body but becomes latent and may be reactivated by stress or inflammation. Repeated immune responses to these reactivations causes more inflammation and wears out the immune system resulting in diseases of aging (eg: cardiovascular disease). Here we investigate which aspects of the immune system can control CMV in healthy people and in renal transplant recipients. We focus on a population of cells called natural killer (NK) cells.Read moreRead less
Lymphoid Organ Development: Synthetic Organogenesis Of Artificial Spleen And Characterisation Of Tissue-specific Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$350,232.00
Summary
Spleen is an organ which filters blood circulating around the body and provides immune protection against blood-borne pathogens. Research into spleen development will attempt to synthesise artificial spleen tissue, leading to possible tissue replacement therapies or enhancement of immunity towards infection or cancer. Cellular development in spleen will also be investigated with a view to identifying novel white blood cell subsets that have potential for becoming new targets for immunotherapy.
Cholinergic Abnormalities In Alzheimer's Disease: Identification Of Novel Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$478,500.00
Summary
The aim of this project is to develop new drugs for the treatment of Alzheimer's disease. Alzheimer's disease is a disease of ageing commonly associated with memory loss. The disease is caused by the build up of amyloid protein in the brain. However, it is not known how amyloid protein causes degeneration of normal brain function. Our previous studies have shown that amyloid protein targets two components which are important for normal brain function. These components are 1) acetylcholinesterase ....The aim of this project is to develop new drugs for the treatment of Alzheimer's disease. Alzheimer's disease is a disease of ageing commonly associated with memory loss. The disease is caused by the build up of amyloid protein in the brain. However, it is not known how amyloid protein causes degeneration of normal brain function. Our previous studies have shown that amyloid protein targets two components which are important for normal brain function. These components are 1) acetylcholinesterase and 2) nicotinic receptors, which are known to be important for memory. The aim of this application is to identify the mechanisms by which amyloid protein targets acetylcholinesterase and nicotinic receptors and to design inhibitors of this interaction which may ultimately provide a platform for future drug development.Read moreRead less
The Effect Of Selected Nutraceuticals On Brain Blood Vessels And Memory.
Funder
National Health and Medical Research Council
Funding Amount
$445,206.00
Summary
The human brain receives 1000L of blood per day, distributed through minute vessels called capillaries. The integrity and function of brain capillaries is compromised with aging and this may contribute to memory disturbances. Our laboratory has identified several naturally occurring compounds that prevent age-associated defects of brain capillaries. The primary aim of this project is to explore if these agents are beneficial for restoring brain capillary function and memory.