As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
Examining The Importance Of DNA Damage Repair For Oocyte Quality, Female Fertility And Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
The Role Of Nuclear Architecture In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$561,966.00
Summary
The goal of the proposed research is to understand how dynamic changes to the chromatin genome packaging network, interact with the DNA damage response and gene expression machinery, to repair damaged DNA and the impact this has on cancer biology. To do so we are combining cutting edge molecular biology techniques with innovative novel microscopy methods developed by our research team, that far exceed the spatiotemporal resolution currently used to study chromatin biology.
How Replication Stress Activates The Mitotic Telomere DNA Damage Response To Kill Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$486,467.00
Summary
We discovered a novel mechanism linking stress during DNA replication to difficulties with the cell division process, and identified how this turns on DNA damage response signals from the chromosome ends (i.e. “telomeres”). We have further identified that we can exploit this mechanism to kill cancer cells. In this project we will explore this newly discovered mechanism and identify how it can be targeted for therapeutic purposes.
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.
Liquid Biopsy For Personalised Monitoring Of Melanoma Patients
Funder
National Health and Medical Research Council
Funding Amount
$820,888.00
Summary
Despite the success of recent melanoma treatments, therapies are effective long term in only a proportion of patients. Here we will progress preliminary findings in collaboration with biotechnology and pathology companies to develop highly effective companion biomarkers that will aid treatment decisions throughout disease course. Our team will spearhead translation of these markers into the clinic for routine monitoring of melanoma patients.
Understanding Mitochondrial DNA Segregation And Transmission.
Funder
National Health and Medical Research Council
Funding Amount
$512,449.00
Summary
We inherit our mitochondrial DNA from our mothers. Mutations to mitochondrial DNA can give rise to severely debilitating diseases that can be passed from one generation to the next. The aims of this application are to understand how mutant mitochondrial DNA is selected for; when it affects energy production during development; and to ensure that certain reproductive strategies do not result in the adverse transmission of mitochondrial DNA that will affect subsequent generations.
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.
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
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.