A Novel Viral Modifier Of TNF Family Receptor Signalling: Elucidation Of Mechanisms Of Action
Funder
National Health and Medical Research Council
Funding Amount
$453,727.00
Summary
Over millions of years, viruses have evolved a great number of strategies to allow them to subvert the effectiveness of the host response. We have discovered that one of these viral strategies seems designed to block the synthesis of an important anti-viral factor, called tumour necrosis factor. In this project, we aim to work out how the viral factor blocks tumour necrosis factor production inside the cell, at the level of the molecules involved. The second aspect of this project concerns the i ....Over millions of years, viruses have evolved a great number of strategies to allow them to subvert the effectiveness of the host response. We have discovered that one of these viral strategies seems designed to block the synthesis of an important anti-viral factor, called tumour necrosis factor. In this project, we aim to work out how the viral factor blocks tumour necrosis factor production inside the cell, at the level of the molecules involved. The second aspect of this project concerns the identification of the types of cells and responses which the viral factor acts upon to manipulate the host response. We reason that this information will improve our understanding of how tumour necrosis factor production is regulated and the significance of this type of response in virus infection and physiology, more generally. The application of this research will be to aid the design of better drugs for the treatment of many conditions where tumour necrosis factor production contributes significantly to pathology, eg rheumatoid arthritis and autoimmunity. In some conditions, it may be a therapeutic advantage to selectively turn on tumour necrosis factor, eg for treatment of infections or cancer.Read moreRead less
Towards Selective Targeting Of HDACs For Anti-inflammatory Applications
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
HDAC inhibitors are anti-cancer drugs that kill rapidly growing cells (like cancer cells). These drugs also have anti-inflammatory properties and so may be beneficial in chronic inflammatory diseases such as as Rheumatoid Arthritis. However, it is unknown how they reduce inflammation. In this project we aim to understand how HDAC inhibitors act as anti-inflammatory agents and to design new HDAC inhibitors with reduced side effects for the treatment of inflammatory diseases.
What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.
Proatherogenic CD4 NKT Cells And Atherosclerosis: Molecular Mechanisms And Therapeutic Strategies For Suppression
Funder
National Health and Medical Research Council
Funding Amount
$504,348.00
Summary
Immune cells called CD4+ iNKT cells are known to be activated by lipids which initiate development of atherosclerosis, a disorder of blood vessels which is responsible for most heart attacks and strokes. We aim to investigate how these cells contribute to the development of this important blood vessel disoder and examine potential ways of inhibiting their activation to prevent heart attacks and strokes.
Natural Killer (NK) Cells And Development Of Atherosclerosis: Cellular And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
Atherosclerosis, the accumulation of fat and white cells in the blood vessel wall is the major cause of heart attacks, stroke and death. Cholesterol lowering drugs reduce the risk by only 40%. Targeting cells that promote inflammation is one approach to further reduce risk. We have shown that a specific cell type called a natural killer (NK) cells contributes greatly to development of atherosclerosis. Our aim is to understand how these cells promote development of atherosclerosis.
Protease Activated Receptor 2 Antagonist In Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,347.00
Summary
The immune response to infection involves a network of proteins that produce an inflammatory response. Sometimes this response is prolonged or uncontrolled and can lead to a large number of inflammatory and other diseases. We have discovered a class of drugs that can bind to a particular protein on the surface of human cells and control this inflammatory response. This property has the potential to treat a wide range of inflammatory and other diseases in humans.
Prof McGuckin is studying common chronic diseases (gut and respiratory inflammatory diseases, arthritis, and obesity and diabetes) that are major contributors to poor health in the Australian community and are major contributors to healthcare expenditure. His research includes basic studies elucidating the biological basis of these diseases and then uses this new knowledge to develop new therapeutic approaches to treatment. The new therapeutic approaches will be tested in model systems as a prel ....Prof McGuckin is studying common chronic diseases (gut and respiratory inflammatory diseases, arthritis, and obesity and diabetes) that are major contributors to poor health in the Australian community and are major contributors to healthcare expenditure. His research includes basic studies elucidating the biological basis of these diseases and then uses this new knowledge to develop new therapeutic approaches to treatment. The new therapeutic approaches will be tested in model systems as a prelude to clinical trials.Read moreRead less
Activated Platelets As Unique Targets For Early Imaging And Site-directed Therapy Of Cardiovascular And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$846,979.00
Summary
Heart attack and inflammatory diseases such as rheumatoid arthritis und multiple sclerosis either kill or severely disable people. We use the presence of platelets early on in these diseases to develop methods for early diagnosis as well as potential drugs for site-directed therapy. We have developed new biotechnological tools to perform novel high sensitivity imaging in Positron Emission Tomography (PET) and laser light imaging as well as a localised anti-inflammatory therapy.