The Role Of LINE Encoded Natural Antisense Transcripts In Immune Regulation
Funder
National Health and Medical Research Council
Funding Amount
$934,853.00
Summary
Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. This proposal aims to utilize cutting edge genomic technologies to generate new knowledge about how the non-coding genome regulates the expression of protein coding genes in human autoimmune disease.
Improving The Diagnosis Of Disorders Sex Development (DSD)
Funder
National Health and Medical Research Council
Funding Amount
$818,997.00
Summary
Disorders of sexual development (DSDs) are surprisingly common, and often result in genital abnormalities, gender mis-assignment, infertility and psychological trauma. We will use our expertise in human genetics, molecular cell and developmental biology, to find genes important for sex development, identify gene defects that cause DSD, and study their functions. We will liaise with clinicians to apply these findings to the accurate diagnosis and medical care of DSD in children.
Bushfire Smoke Exposure During Pregnancy And Epigenetic Changes In Offspring
Funder
National Health and Medical Research Council
Funding Amount
$1,707,578.00
Summary
The Australian bushfire season of 2019/2020 was unprecedented in terms of length and intensity, and a question of significant importance to public health for the community is whether exposure to bushfire smoke has long term impacts on children whose mothers were pregnant at the time. This grant investigates a potential mechanism called epigenetics (which changes the way genes are expressed in response to environmental conditions), in newborns whose mothers were exposed to bushfire smoke.
Analysis Of The Osteoclast Methylome For Characterisation Of Epigenetic Mechanisms Underlying Metabolic Bone Disease
Funder
National Health and Medical Research Council
Funding Amount
$299,018.00
Summary
A large number of genetic variants have been identified that have a role in osteoporosis, however for many of these, the mechanism by which they influence the disease remains to be determined. This study will fill a critical knowledge gap by investigating the epigenetic control of gene expression in osteoclasts (bone resorbing cells). This research will generate a unique international resource that will provide foundation data to understand and treat this prevalent and debilitating bone disease.
Ataxia-Telangiectasia: An Emerging Role For Inflammation In Driving Neurodegeneration And Premature Ageing
Funder
National Health and Medical Research Council
Funding Amount
$437,436.00
Summary
Ataxia-Telangiectasia (A-T) is a devastating genetic disease that arises in early childhood and causes patients to die in their twenties. To date there is no cure, and therapeutics are desperately needed. This project will use state-of-the-art brain organoids derived from stem cells of A-T patients in order to better understand this disease and evaluate novel drugs that target the molecular mechanisms that drive chronic inflammation and brain neurodegeneration in children with A-T.
Epigenetic Biomarker Discovery For Cardiovascular Disease Risk Stratification Of Women Following Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$1,275,101.00
Summary
Those women whom have suffered from severe complications during pregnancy have an increased risk of developing heart disease. This increased risk may be due to epigenetic changes during pregnancy that alter the expression of specific genes. These epigenetic changes persist after birth and increase heart disease risk for these women. This project seeks to evaluate those epigenetic changes associated with severe pregnancy complications predicting heart disease in a large group of Australian women.
Understanding The Molecular Mechanisms Of Cell Death In Radiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$643,856.00
Summary
Radiotherapy (RT) is responsible for 40% of cancer cures. New technology enables RT delivery in fewer treatments using higher radiation dosages through a technique called 'ART'. While ART is effective in the clinic, the underlying mechanisms of cancer cell death are unclear. Here we show that ART induces two distinct waves of cancer cell death. We will characterize these waves of cell death and determine how to enhance tumour cell killing with pharmacological intervention.
Understanding The Role Of DNMT1 SUMOylation In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$639,290.00
Summary
Most cancers have abnormally high levels of DNA methylation, which turns off cell death genes, making cancer cells immortal. We have a new drug, called DNMT1i, that targets this feature of cancer cells and we recently found a new drug target that enhances the activity of DNMT1i. Our research will determine how these two drugs synergise to effectively kill cancer cells and will justify their use in clinical trials, which we believe will improve outcomes for patients with cancer.
UNDERSTANDING THE BENEFITS AND LIMITATIONS OF METAPHASE II SPINDLE TRANSFER
Funder
National Health and Medical Research Council
Funding Amount
$1,629,373.00
Summary
Mitochondrial DNA (mtDNA) diseases are transmitted from a mother's eggs to her children. However, the levels of affected mtDNA differ amongst her eggs. Consequently, a carrier would not know if the newborn child were to suffer from these diseases. Mitochondrial Donation offers couples the potential to have an unaffected child. We will undertake the most comprehensive study of mitochondrial donation using one of its associated approaches to determine if it produces healthy embryos and offspring.