The Mutagenic Influence Of 5-methylcytosine And Its Relevance For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$844,462.00
Summary
Over time our cells accumulate damage to their DNA, which introduces mistakes in the genetic code. These mistakes can alter genes that regulate cell growth and survival and, in this way, they begin the process of turning a normal cell into a cancer. This research is investigating the cellular repair mechanisms that safeguard against DNA damage. Manipulating these repair mechanisms may offer a new way to treat cancer, by selectively inducing DNA damage within cancer cells.
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.
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.
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
Deciphering The Role Of DNA Methylation In The Regulation Of Alternative Splicing
Funder
National Health and Medical Research Council
Funding Amount
$865,494.00
Summary
When a gene is turned on, the messenger RNA must be correctly processed to generate functional proteins. This ‘splicing’ process is essential for normal cellular activity, and is disrupted in many human diseases. We have discovered that an epigenetic modification, DNA methylation (mC), may control splicing. This project will investigate how mC influences splicing and use new epigenome-editing tools to control it, in order to ultimately understand and treat diseases involving aberrant splicing.
Epigenetic Reprogramming Within The Pluripotent Lineage Of The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$663,050.00
Summary
Cells of the early embryo have the remarkable capacity to form all of the different tissues and organs in the body. This property requires re-organisation of the embryo’s genetic material in a manner analogous to re-booting a computer. This project will define the properties of this rebooting process. This information will allow much better strategies for building spare parts for regenerative medicine and provide the information required to reduce the incidence of inborn defects.
Novel DNA Modifications Underlying Sex Differences In Fear-related Learning And Memory
Funder
National Health and Medical Research Council
Funding Amount
$531,978.00
Summary
Women are at increased risk of developing fear-related anxiety disorders. We have recently discovered that there sex-specific regulatory mechanisms in the brain that are associated with differences in the control of fear. In this proposal, we will determine whether novel DNA modifications in the female brain are responsible for establishing sex differences in brain states that make the brain more or less responsive to fear-related learning.
Leveraging Genomics Strategies To Generate Adult Neurons From IPSCs And Somatic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,593,336.00
Summary
Recent advances have made it possible to derive myriad specialized human cells from stem cells or by directly reprogramming cell identity. However, these derived cells are generally arrested at a fetal developmental stage, and do not mature to function like adult cells. We will use new genomic, epigenetic, cell reprogramming, and manipulation methods to discover how to derive mature cells, aiming to generate mature neurons for use in neurobiology research, disease modeling, and drug screening.
EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.