Targeting Bone Marrow Lesions To Find Interventions In The Progression Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$467,395.00
Summary
It is essential to elucidate the underlying cause(s) of osteoarthritis because our current level of understanding of this condition has failed to produce effective treatments. Lesions in the bone under the cartilage (BMLs), seen using MRI, have strong potential value for the objective monitoring and management of OA. However, because the nature of BMLs is not well understood, the aim of this application is to perform a comprehensive study of BMLs in OA bone.
Understanding Epigenetic Modification During Oogenesis For Novel Treatments Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Infertility affects about 10% of Australian women and the success rates of current infertility treatments are low due to our poor knowledge of eggs development. The numbers of obese and older women trying to conceive are increasing; fertility treatments are even less effective for them. I have generated mouse models to elucidate the pathways regulating egg development. I will study for alterations in these pathways in the mouse models which perfectly mimic the obesity and aging in women.
Identifying Novel Lipid And Genetic Signatures Of Metabolic Disease In Early Childhood
Funder
National Health and Medical Research Council
Funding Amount
$354,592.00
Summary
Both our genetic makeup and environment can contribute to the development of obesity, diabetes and heart disease. Although onset usually occurs in adulthood, the progression towards disease can start in early life. Early childhood represents an opportunity for intervention to avoid adverse health outcomes in adulthood. This proposal combines two established birth cohorts from Singapore (GUSTO) and Australia (BIS) to examine the genetic and environmental origins of metabolic diseases.
Improving Physical Health Outcomes For Young People With Psychotic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$189,384.00
Summary
Enduring psychotic disorders are associated with a reduced life expectancy by 25 years, which is mainly due to cardiovascular disease. This project will produce a training package that will improve clinician’s skills and knowledge of screening and treatment for physical health risk factors in young people with psychosis. This project will result in the development of an intervention for reducing the prevalence of these cardiovascular risk factors known to contribute to this early mortality.
The Management To Optimise Diabetes And MEtabolic Syndrome Risk Reduction Via Nurse-led Intervention (MODERN) Study
Funder
National Health and Medical Research Council
Funding Amount
$1,445,861.00
Summary
There is increasing recognition of society’s responsibility to provide effective and sustainable health care to the entire population and not just selected parts. This practical study will test the impact of a nurse-led, multidisciplinary prevention program to reduce the risk of future cardiovascular events in middle-aged individuals at a high risk of developing cardiovascular disease (CVD) living in regional Australia.
Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.
Targeting The Sympathetic Nervous System To Reduce The Burden Of Fatty Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$728,152.00
Summary
The metabolic syndrome is characterised by abdominal obesity, high blood pressure and an increased risk of diabetes development. It is clear from our own observations that the sympathetic nervous system (SNS) is important in the generation of obesity-related illness and, through its stimulation of the liver, plays an important role in the development of obesity-related liver disease. We will target the SNS in order to reduce the burden of obesity-related liver disease.
The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Early Nutrition, Epigenetics And Developmental Outcomes In Children.
Funder
National Health and Medical Research Council
Funding Amount
$550,093.00
Summary
Increasing evidence demonstrates that early nutrition, including in pregnancy, has long lasting programming effects on later health of children. Evidence implicates epigenetics (literally ‘above DNA’) in mediating these effects. The most convincing data exists for obesity and related disorders such as metabolic syndrome, diabetes, and heart disease. The focus of this project is on understanding how ‘epigenetic’ mechanisms are influencing the way our genes function to cause these disorders.