Cellular And Molecular Determinants Of Preleukaemic And Leukaemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$292,635.00
Summary
It has recently become evident that the formation, growth and relapse of many cancers is driven by a rare population of cancer stem cells (CSCs) that have the unique ability to propagate new tumours and are highly resistant to current therapies. However, which normal cells are transformed into CSCs is not known. We will take a potent cancer gene found in leukaemia, and switch it on and off in specific blood cells in mice to determine which healthy cells can be turned into leukaemic stem cells.
A New Animal Model Of The Prodrome In Schizophrenia. Enhanced Dopamine In Prodromal Schizophrenia (EDiPs)
Funder
National Health and Medical Research Council
Funding Amount
$571,990.00
Summary
Psychiatrists now recognize a pre-symptomatic stage is present in people at risk of developing schizophrenia. Using new brain imaging techniques we now know that some of these individuals have changes in a major neurotransmitter, dopamine, prior to being diagnosed. We have developed a new model in animals, which recreates these exact same changes at a comparable age. We want to now understand what are the broader effects in the brain and try and block these changes in dopamine with new drugs.
The Australian Phenome Bank will establish a frozen sperm bank, database, and training program to enable access by the research community to new strains of genetically modified mice. Efficient access to diverse strains, provided by the Phenome Bank, will be critical for translating the human genome sequence into an understanding of specific mechanisms regulating all the body organ systems in health and disease, and for developing new disease prevention and treatment approaches.
Preventing The Transition From Acute To Chronic Pain. The Role Of Neural And Non-neural Factors.
Funder
National Health and Medical Research Council
Funding Amount
$2,998,900.00
Summary
Pain following injury usually dissipates as the injury heals, however in some individuals it persists and lasts for years. Chronic pain is extremely difficult to treat, particularly that which originates from a damaged nerve. One of the roadblocks in developing effective treatments is our limited understanding of the pathophysiology. The overall aim of this proposal is to address this gap and determine the processes that occur in the brain that results in acute pain transitioning to chronic.
How Important Is Collagen Destruction In Arthritis? A Study With Collagenase-resistant Knockin Mice
Funder
National Health and Medical Research Council
Funding Amount
$529,723.00
Summary
Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is n ....Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is not known whether inhibiting aggrecanases is sufficient to block cartilage damage long-term. In contrast, other studies suggest that aggrecan is only lost after damage to the collagen scaffold. These studies propose that clipping of the collagen scaffold may initiate aggrecan release; with progressive degeneration and collagen clipping, more aggrecan is lost, until ultimately the scaffold is severely damaged and aggrecan is severely depleted. Cartilage can only withstand a limited degree of collagen degradation and any significant damage to the network is widely considered to be irreparable. It is unclear what role aggrecanases and collagenases have in initiating and perpetuating cartilage damage. We have mice with aggrecan resistant to aggrecanases and mice with inactive aggrecanase. We will also create mice with collagen resistant to collagenase. We will use these mice to determine the contribution of collagenases and aggrecanases to the initiation and progression of cartilage damage, in three models of joint disease. We will identify differences in time of disease onset, rate of disease progression and disease severity. The results will show whether one or both activities is important for the initiation and progression of joint disease. This will reveal whether single or combination therapies are required for the management of arthritis. The research will inform the pharmaceutical industry on directions for the development of new drugs to prevent joint disease.Read moreRead less
I am a neuroscientist using robust statistical methods to identify effective neuroprotectants for stroke. I am examining the use of neuroprotection and novel imaging approaches to extend the utility of thrombolysis, and testing the hypothesis that neuropr
This proposal aims to examine how the oral bacterial pathogen, P.gingivalis, interacts with the host to worsen the severity of disease in rheumatoid arthritis. We propose a new mechanism whereby the pathogen directly activates a major destructive host pathway to promote tissue and bone destruction, which are two of the clinical hallmarks of rheumatoid arthritis. We also propose that this host-pathogen interaction occurs in periodontal disease.
The National Centre For Asbestos Related Diseases (NCARD)
Funder
National Health and Medical Research Council
Funding Amount
$2,500,000.00
Summary
The National Centre for Asbestos Related Diseases is a world-leading centre studying the deadly cancers mesothelioma and lung cancer. Our ongoing Centre of Research Excellence program includes research from the development and genetics of asbestos-related cancers, through to new treatments, novel ways of imaging cancer, and the supportive care of people with these cancers. This program will improve the detection, diagnosis, and treatment of mesothelioma and asbestos-related lung cancer.
Neuroprotection Against Parkinson’s Disease With Remote Photobiomodulation
Funder
National Health and Medical Research Council
Funding Amount
$314,818.00
Summary
Treating the head of rodents with low-intensity 670nm light protects against Parkinson’s disease (PD), but the large size of the human skull and brain precludes clinical translation of this treatment. We have discovered that the brain is also protected when light is targeted at peripheral tissues (e.g. a limb), overcoming problems of delivery. This project aims to optimise this treatment and better understand how it works, to lay the scientific basis for a clinical trial.