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.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Prion-like Behaviour In Immunity: Super-sized Signalling Platforms?
Funder
National Health and Medical Research Council
Funding Amount
$611,995.00
Summary
Prions have been mostly associated with pathologies but recent discoveries show that prion-like behaviour may be beneficial, enhancing our immune response for example. To test this, we want to systematically explore all human proteins involved in the defence against pathogens, find new prion-like trends and probe their role in the innate immune response.
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.
Development Of A New High Throughput Screen For Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$351,320.00
Summary
Inadvertent drug block of hERG, a potassium channel in the heart, can cause cardiac arrhythmias and sudden cardiac death. Screening for hERG toxicity has become a major hurdle for development of new drugs. We will use a mutant hERG protein that has enhanced drug binding to develop a high throughput test for hERG toxicity. Identification of dangerous drugs early in the drug discovery process will save the pharmaceutical industry millions of dollars in the costs of brining new drugs to market.
Centre Of Research Excellence In Medicines Intelligence
Funder
National Health and Medical Research Council
Funding Amount
$2,500,000.00
Summary
The NHMRC Centre of Research Excellence in Medicines Intelligence is a co-ordinated research program that will accelerate the development and translation of evidence on prescribed medicines use and outcomes for regulators and payers. The CRE is perfectly placed to embrace the national ‘call to action’ from the Health Minister's recent announcement to establish Quality Use of Medicine Safety as a National Health Priority.
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
Circulating Tumour DNA To Monitor Treatment Response And Resistance In Chronic Lymphocytic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$876,950.00
Summary
Many cancers shed small amounts of DNA (ctDNA) into the patient’s bloodstream and recent advances in genomic technologies now allow levels of ctDNA to be accurately measured in the blood. Changes in ctDNA levels have potential to be used as specific markers of disease progression and/or response to cancer therapy. This project will evaluate if ctDNA can be used to monitor treatment responses and individualise treatment decisions in patients with chronic lymphocytic leukaemia.