Determining The Clinical Effectiveness Of Antiviral Drugs Against Oseltamivir- And Laninamivir-resistant Influenza Viruses In Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$388,067.00
Summary
Currently, the neuraminidase inhibitors are the only drugs that are effective against seasonal influenza viruses. However, viruses can develop resistance to these drugs. Using viruses with varied levels of resistance, the project will determine the effectiveness of different drug treatments in animal models. This will lead to better treatment for those patients seriously ill with drug-resistant influenza viruses.
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
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.