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.
SETD7-dependent Regulation Of Hippo/YAP And Wnt/beta-catenin Pathways In The Intestine
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
Colon cancer accounts for approximately 10% of all cancer-related deaths in Australia. One of the most common causes of colon cancer is a mutation in a signalling pathway called the Wnt/beta-catenin pathway. Despite this knowledge, there are currently no drugs that directly target this pathway to treat colon cancer. We have now identified a new way to control this pathway and have developed a potent and specific drug to block activation of this pathway.
Deciphering The Role Of Atypical DNA Methylation In Neuronal Genome Regulation And Neurological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$773,484.00
Summary
This research will use a combination of genomic, biochemical and functional genomics approaches to investigate the role of the atypical mCH form of DNA methylation in neuronal genome regulation and function, and provide new insights into the role of the epigenome in healthy brain function and neural pathologies.
This study will address the idea that cancer commonly involves a genetic pathway that is normally used by stem cells to proliferate in an undifferentiated state. We have evidence to indicate that this system is active in cancer cells and believe this could explain how cancer cells manage to divide rapidly in a primitive state. This project may bring a new perspective to the study of malignant transformation and has the potential to reveal multiple new targets for cancer therapy.
Novel Ways Of Utilizing Genome-wide DNA Methylation Data From Peripheral Blood Samples In Genetic Epidemiology
Funder
National Health and Medical Research Council
Funding Amount
$285,186.00
Summary
The aim of this project is to develop statistical methods and paradigms to better leverage the considerable amount of peripheral blood DNA methylation data that has been collected from large scale epidemiological studies. In particular, our focus is on developing and optimizing statistical methods of using DNA methylation profiles to “tag” environmental exposures, so that this information can be better utilized to investigate the genetic and environmental basis of complex traits and diseases.
Epigenetic Regulation Of Cell Lineage Differentiation In The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$440,983.00
Summary
Exposure of embryos to a range of stresses can increase the predisposition to chronic diseases of adulthood. Stressing embryos at critical stages of development cause errors in reorganization of the nucleus that are required for normal gene expression. These errors are propagated into adulthood. This project will map the normal processes of nuclear reorganization and define how stress to the embryo changes this process, allowing an understanding of the causes of some important chronic diseases.
FIELD LIFE: Lifestyle Interactions In Fenofibrate And The Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$1,071,754.00
Summary
Genetic and environmental factors influence the risks of developing the blood vessel (vascular), eye and kidney complications of diabetes, but how extensively these factors interact is less well understood. We will examine blood levels of a new class of regulatory molecules (called microRNAs), and of DNA damage and identify how they are linked to vascular risk factors, and heart, foot, eye and kidney damage in 2000 well-characterised Australians with type 2 diabetes from the FIELD Study.
KRAS- And BRAF-Mediated Methylation Signatures In Colorectal Cancers And Polyps
Funder
National Health and Medical Research Council
Funding Amount
$457,076.00
Summary
Bowel cancer is one of the most common cancers affecting Australians. We hypothesise that there are different types of bowel cancer depending on different genes that can be inactivated abnormally, and these subgroups have different clinical features and responses to therapy. We aim to identify the major gene changes that characterise these subgroups, which will in the future allow the development of gene markers for early detection as well as the possibility of individualised patient therapy.
Epigenetic Changes In The Prostate Cancer Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$848,954.00
Summary
Many men with prostate cancer have slow-growing tumours that are unlikely to spread outside the prostate. These men with low-risk cancer are often monitored to prevent unnecessary aggressive treatments. However, the current methods used to distinguish between slow-growing and aggressive tumours are imprecise and there is a risk of missing aggressive tumours. We aim to identify new biomarkers of prostate cancer by measuring modifications to the DNA in the tumour and surrounding cells