CTCF is a unique architectural protein that regulates the three-dimensional (3D) folding of the genome to switch our genes on, or off. This is important, as it affects how DNA is arranged inside the cells, which is turn assures correct gene expression patterns. Here, we will define the role of CTCF in organizing the 3D genome architecture and identify genetic and epigenetic states that control its function.
Four Dimensional Epigenome Remodelling: Implications For Endocrine Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$828,560.00
Summary
Patients with estrogen receptor positive breast cancer receive endocrine therapy, however half fail to respond and relapse. Endocrine resistant breast cancer currently represents the most significant challenge to breast cancer treatment. We suggest that three-dimensional epigenetic remodelling is an underlying mechanism that determines endocrine sensitivity that we will exploit as a novel therapeutic strategy to effectively treat patents with recurrent disease.
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.