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.
Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less
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.
Centre For Clinical Research Excellence In Respiratory And Sleep Medicine
Funder
National Health and Medical Research Council
Funding Amount
$2,200,000.00
Summary
The CCRE will enhance Australia's international research reputation in clinical respiratory and sleep medicine by enhancing links between hospital-based investigators. This will foster development of new clinical researchers in these fields. Major research projects will include reducing side effects of asthma therapy in the elderly, better and cheaper ways of diagnosing disorders such as sleep apnoea and blood clots in the lung, keeping patients with chronic lung diseases out of hospital and avo ....The CCRE will enhance Australia's international research reputation in clinical respiratory and sleep medicine by enhancing links between hospital-based investigators. This will foster development of new clinical researchers in these fields. Major research projects will include reducing side effects of asthma therapy in the elderly, better and cheaper ways of diagnosing disorders such as sleep apnoea and blood clots in the lung, keeping patients with chronic lung diseases out of hospital and avoiding accidents due to lack of sleep.Read moreRead less
Long-term Nerve Damage In Cancer Survivors: Identification Of Risk Factors And Optimal Assessment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$850,172.00
Summary
Nerve damage following chemotherapy treatment leads to early treatment cessation and long-lasting disability, developing with commonly used chemotherapies. There is a critical need to understand the mechanisms, optimize clinical assessment and develop interventions to prevent nerve damage. This project is designed to detect the impact of long-term nerve damage in cancer survivors and develop a risk profile based on clinical, neurophysiological and genetic factors.
We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other co ....We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other countries (in North and South America, Asia, and Europe). This study will provide the first nationally-representative information on the burden of chronic obstructive pulmonary disease (COPD) and the opportunities for health gain by improving the management of this illness. In Australia, COPD is a relatively silent and under-recognised disease but nevertheless is the third most important contributor to the burden of disease and the third leading cause of hospital admission as well as being the underlying cause of 4.2% of all deaths. The information we will collect is needed to form a basis for prevention and disease management interventions to reduce the burden of COPD, particularly among population sub-groups who are disproportionately affected, either due to greater exposure to risk factors (mainly tobacco smoking and occupation), greater susceptibility, under-recognition and under-diagnosis, or inadequate disease management. Importantly, the study will serve to raise awareness about the hazards of smoking for all Australians. By identifying target groups, prevalent exposures and management deficiencies, it will lead the way towards policy-relevant randomised controlled trials testing community-based interventions to prevent COPD and-or manage it more effectively. The information collected will help advance knowledge of the prevalence, burden and treatment of COPD that will be relevant to communities throughout the world.Read moreRead less
The Clinical Utility Of Small Airway Function Tests In Paediatric Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Respiratory disease is an important child health issue with long term implications into adulthood. The evaluation of small airways involvement in disease processes, using an accurate sensitive measures of function, such as forced oscillation technique and multiple breath washout, potentially facilitates not only early detection of disease, but instigation of earlier treatment, better assessment of response to treatment, and ultimately better outcome.
Implementing Evidence Into Practice To Improve Chronic Lung Disease Management In Indigenous Australians: The Breathe Easy, Walk Easy-Lungs For Life (BE WELL) Project
Funder
National Health and Medical Research Council
Funding Amount
$780,089.00
Summary
The burden of chronic obstructive pulmonary disease (COPD) in Indigenous Australians far exceeds that in non-Indigenous Australians. The project will evaluate whether the BE WELL program can build the capacity of Aboriginal health workers to provide affordable and effective management of COPD, including pulmonary rehabilitation. This program will improve health outcomes, reduce hospital admissions and address the poor access to best-practice management of COPD in Indigenous communities.
Breathe Well: Improving Cancer Imaging And Targeted Radiotherapy Using Audiovisual Biofeedback
Funder
National Health and Medical Research Council
Funding Amount
$606,847.00
Summary
Irregular breathing causes anatomical errors in medical images and consequently cancer targeting accuracy, resulting in poorer clinical outcomes and increased health care costs. We have developed and patented the Breathe Well Audio Visual (AV) biofeedback device, to improve breathing regularity. Our goal is to gather critical scientific information and reach commercial proof-of-concept objectives that will allow us to attract investment to establish a viable medical device enterprise.
The Use Of Gene-Silencing Nanodrugs To Inhibit Lung Cancer Growth
Funder
National Health and Medical Research Council
Funding Amount
$452,950.00
Summary
Lung cancer accounts for the most cancer deaths worldwide. This research proposal will use state-of-the-art nanomedicines designed to penetrate lung tumours and suppress a gene which drives cancer growth and resistance to chemotherapy drugs. Our results could underpin new approaches that revolutionise more effective and less toxic treatments for a highly lethal malignancy.