Defining The Plasma Methylome To Guide Melanoma Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
This project aims to characterise circulating methylation patterns (chemical modifications to DNA) from the blood of melanoma patients. Through this ground-breaking research, I will establish a minimally-invasive and simple blood test that will predict response and resistance from treatment, provide a greater understanding of the disease, reshape the treatment management of melanoma patients and lead to improved patient outcomes.
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.
Epigenetic Signatures Of Abnormal Adult Neurogenesis In Rett Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$869,332.00
Summary
Rett syndrome (RTT) is a severe neurodevelopmental condition arising in early childhood. In Australia, RTT affects an estimated 1/8500 females. The vast majority of RTT patients carry a single mutation in the gene MeCP2. Recent advances in genetic engineering may allow MeCP2 mutations to be corrected in patients. This study will assess whether other molecular factors are involved in the RTT phenotype in patient neurons, and whether these factors are likely to be corrected by MeCP2 gene therapy.
Epigenetic Predictors Of Outcome In Malignant Glioma
Funder
National Health and Medical Research Council
Funding Amount
$697,720.00
Summary
Human high grade gliomas (HGG) present as heterogeneous disease, primarily defined by the histologic appearance of the tumor cells.Glioblastoma multiforme (GBM) is the most common illness and continues to have a very poor prognosis, despite the use of multimodality therapy including surgery, radiation therapy and chemotherapy. We will use our existing biobank of specimens, clinical information and molecular investigation to identify factors that determine outcomes.
One of the interesting questions in human biology is why monozygotic twins, which have an identical genetic make up, can still vary in many complex traits such as height, eye colour and susceptibility to various mental and disease states. It is clear that this variation is not always due simply to environment. We propose in this application to show that, even if the genetic code is identical in monozygotic twins, epigenetic marks such as DNA methylation and histone modifications can vary between ....One of the interesting questions in human biology is why monozygotic twins, which have an identical genetic make up, can still vary in many complex traits such as height, eye colour and susceptibility to various mental and disease states. It is clear that this variation is not always due simply to environment. We propose in this application to show that, even if the genetic code is identical in monozygotic twins, epigenetic marks such as DNA methylation and histone modifications can vary between critical genes giving rise to differences in gene expression patterns. We propose that the variation in the methylation pattern arises after the two embryos have split, at a time when the developing embryo undergoes genome-wide demethylation followed by de novo re-methylation. The importance of this project is NOT what it tells us about twins themselves, but that twins can provide the clue to disease processes which affect everybody in the population. The results of these experiments will determine the extent to which epigenetic changes to the genome that occur early in embryonic development provide an additional source of variation in gene expression that could contribute to phenotypic variation. By using identical twins we eliminate the possibility that epigenetic modifications that we observe are themselves influenced by genotype. Determining these epigenetic differences will provide an insight into the mechanisms underlying complex traits and human disease.Read moreRead less
In this grant we aim to study the moecular basis of cancer. The promoter regions of tumour suppressor genes are often modified in cancer by a chemical process called methylation. Methylation of DNA is associated with gene silencing. Therefore DNA methylation is commonly regarded as causing the silencing of genes in cancer. In this grant, we aim to determine if methylation is causal in triggering gene silencing in cancer, or if methylation is a consequence of gene silencing. This is a critical di ....In this grant we aim to study the moecular basis of cancer. The promoter regions of tumour suppressor genes are often modified in cancer by a chemical process called methylation. Methylation of DNA is associated with gene silencing. Therefore DNA methylation is commonly regarded as causing the silencing of genes in cancer. In this grant, we aim to determine if methylation is causal in triggering gene silencing in cancer, or if methylation is a consequence of gene silencing. This is a critical distinction in understanding the role of methylation in cancer development.Read moreRead less