The Characterisation Of Deubiquitinating Enzyme A (DUBA) In The Control Of Innate And Adaptive Immune Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$396,041.00
Summary
In response to viruses, the immune system produces interferons. Interferons fight infections but can also contribute to autoimmune diseases, where the body mistakenly attacks itself. Production of interferons is regulated by DUBA. Thus DUBA is an attractive target for therapies against viruses or autoimmune diseases. To achieve this, it is important to understand not only the mechanism of action of DUBA, but also what other roles DUBA may play in the immune system. We can study these in mice.
Regulation Of TNF Receptor Expression By Omega-6 And Omega-3 Polyunsaturated Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
This project looks at two major molecules which our body generates in trying to combat infections, a protein called tumor necrosis factor (TNF) and a fatty acid called arachidonic acid. In some cases the persistent production of elevated amounts of these molecules leads to highly crippling and debilitating diseases , such as rheumatoid arthritis, which pose a huge burden to our community. To develop medication to combat these diseases be it either vaccination or antiinflammatory drugs, there is ....This project looks at two major molecules which our body generates in trying to combat infections, a protein called tumor necrosis factor (TNF) and a fatty acid called arachidonic acid. In some cases the persistent production of elevated amounts of these molecules leads to highly crippling and debilitating diseases , such as rheumatoid arthritis, which pose a huge burden to our community. To develop medication to combat these diseases be it either vaccination or antiinflammatory drugs, there is a need to clearly define key components of the inflammatory response. Since TNF acts through a receptor we propose that a critical issue in the regulation of this inflammatory response is the changes in the expression of these receptors on cells of the immune system. Our preliminary work suggests that lipid molecules such as arachidonic acid (omega-6 fat) interacts with phagocytic cells and causes drammatic changes to the expression of this receptor. Our research proposal will look at this in more detail and place the observation into perspective in terms of parameters of the inflammatory reaction and associated diseases. Furthermore this concept will be examined in relation to the protective effects which the omega-3 fats found in fish oil have on these inflammatory diseases.Read moreRead less
Regulation Of Antiviral And Antiinflammatory Responses By MTNF: Key Role Of Reverse Signaling By Host And Viral TNFR
Funder
National Health and Medical Research Council
Funding Amount
$568,501.00
Summary
New and re-emerging viral infections continue to pose a major problem. We have recently discovered a hitherto unrecognized process that the body uses to regulate its response to infection. Some viruses have evolved to target this process, underscoring its importance. We will study 2 virus models, poxvirus and influenza A, to understand how this process works during infection. We will also examine the potential to exploit this process to block pathology and influence recovery from infection.
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
Structural Investigations Of Bacterial Evasion Of IgA Mucosal And Systemic Immunity
Funder
National Health and Medical Research Council
Funding Amount
$488,812.00
Summary
Nose, throat and skin infections are often caused by streptococcal and staphylococcal bacteria, known as Strep Throat and Golden Staph. Infections can be life-threatening in newborns, the elderly or individuals with weak immune systems. These bacteria make proteins bind and inactivate immune proteins. Our research examines the structural basis for bacterial interactions with a key immune system protein (an antibody called IgA) and may lead to new prevention and treatment strategies.
Cytokines In Milk Modulate The Development Of Immune Responses In The Infant
Funder
National Health and Medical Research Council
Funding Amount
$188,912.00
Summary
There is substantial epidemiological evidence that formula fed infants are more susceptible than breast fed infants to auto-immune diseases later in life. However direct evidence is lacking and the mechanism is not understood. We aim to provide direct experimental evidence to test the hypothesis that maternal milk regulates infant immune responses by providing the factors that modulates antigen presentation and priming in the neonatal gut. The significance of the study lies in the absence of the ....There is substantial epidemiological evidence that formula fed infants are more susceptible than breast fed infants to auto-immune diseases later in life. However direct evidence is lacking and the mechanism is not understood. We aim to provide direct experimental evidence to test the hypothesis that maternal milk regulates infant immune responses by providing the factors that modulates antigen presentation and priming in the neonatal gut. The significance of the study lies in the absence of these regulatory factors in infant formula. The results will allow more fully informed decisions regarding breast feeding, and may lead to the development of infant formula that modulate immune responses in a manner analogous to natural maternal milk.Read moreRead less