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.
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.
The Structural Basis For Promiscuity Of Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$713,035.00
Summary
Special proteins called ion channels control the electrical activity of the heart. Drugs that block ion channels can have the unwanted side-effect of altering the rhythm of the heart beat and causing sudden cardiac death. Extensive efforts are made to screen for this problem during drug development but it is still an inexact science. Here we will use high resolution imaging technologies to get a better understanding of how drugs bind to ion channel proteins.
Targeting Fungal Phospholipid Metabolism For Antifungal Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$828,557.00
Summary
Invasive fungal infections are a serious and escalating health problem. They cause severe disease with a high death rate and are very costly to the health system. New antifungal drugs with novel properties are needed now because there are problems with current drugs. This project aims to develop potent new antifungal drugs that are effective in many fungal diseases and are well-tolerated.
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.
The Social Life of Death. This project aims to investigate experiences of death, dying and bereavement amidst rapid social, economic and political transformation. In the wake of COVID19, and as Australia’s anticipated ‘death boom’ approaches, how to foster good deaths has never been more uncertain, nor more urgent. Drawing on innovative methods and socio-cultural theory, and working in partnership with families and communities, this project aims to generate new knowledge to better inform and imp ....The Social Life of Death. This project aims to investigate experiences of death, dying and bereavement amidst rapid social, economic and political transformation. In the wake of COVID19, and as Australia’s anticipated ‘death boom’ approaches, how to foster good deaths has never been more uncertain, nor more urgent. Drawing on innovative methods and socio-cultural theory, and working in partnership with families and communities, this project aims to generate new knowledge to better inform and improve policy and spark cultural renewal around the end of life. Expected outcomes include setting the international benchmark for novel scholarly understandings of death, dying and bereavement, and centring community voices in addressing contemporary challenges to dying well.
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A Cluster Randomised Controlled Trial Of Nurse And General Practitioner Partnership For Care Of COPD
Funder
National Health and Medical Research Council
Funding Amount
$449,377.00
Summary
Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease that can progress to severe disability and use of hospital services. It is an important cause of both death and disability in Australia. Specifically it is the third leading cause of disease burden after heart disease and stroke. Smoking is the most important cause of the disease and there is strong evidence that smoking cessation will largely prevent progression of COPD. National evidence based guidelines for management of COPD w ....Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease that can progress to severe disability and use of hospital services. It is an important cause of both death and disability in Australia. Specifically it is the third leading cause of disease burden after heart disease and stroke. Smoking is the most important cause of the disease and there is strong evidence that smoking cessation will largely prevent progression of COPD. National evidence based guidelines for management of COPD were published in 2003 but these need to be implemented in the community. General practice is well placed to have a key role in early intervention and evidence based management of COPD. There is evidence that specialised nurses working in collaboration with GPs can improve the care the chronic illnesses including COPD. Care Plans with input from health professionals from a range of disciplines have been recommended for COPD but there are barriers to implementing these in general practice. This project brings together nurse assistance and care planning in a model of care designed to deliver best practice management of COPD in the community. The aim of this research is to evaluate the impact of anurse and GP partnership for care of COPD. We will examine the effect on quality of care and health outcomes at 6 and 12 months follow up. Our hypothesis is that the use of a nurse to work as a team with the patient and GP to develop and implement a care plan based on clinical practice guidelines will improve the quality of care received and have a beneficial effect on the patients' respiratory and overall health. This research will be of major significance for improving COPD care in the community and will have far reaching implications for both policy and practice. It will also define a new role for nurses and GPs working in partnership.Read moreRead less