A Novel Class Of Negative Regulators Of Interleukin-6 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$626,950.00
Summary
Cytokines are protein messengers that activate the immune system to fight infections. When they are too active they cause inflammation and autoimmune diseases so their activity needs to be tightly controlled. We have discovered a new family of regulators (the MARCH proteins) that inhibit cytokine activity by routing cytokine receptors for destruction. We aim to understand how this process works in detail and the role of MARCH proteins in vivo in ameliorating autoimmune diseases.
The Regulation And Function Of Strawberry Notch In Neuroinflammation
Funder
National Health and Medical Research Council
Funding Amount
$733,598.00
Summary
Inflammation is a response to injury and infection that may cause significant damage to the brain. This project will study the regulation and function of a novel gene called strawberry notch that we have identified is a major target of the protein IL-6 which is a central mediator of inflammation in the brain. The findings will advance our understanding of the function of Sbno2 in the context of the actions of IL-6 and will provide crucial new mechanistic insights into a cause of neurological dis ....Inflammation is a response to injury and infection that may cause significant damage to the brain. This project will study the regulation and function of a novel gene called strawberry notch that we have identified is a major target of the protein IL-6 which is a central mediator of inflammation in the brain. The findings will advance our understanding of the function of Sbno2 in the context of the actions of IL-6 and will provide crucial new mechanistic insights into a cause of neurological disease.Read moreRead less
IL-6 Classic And Trans-signalling In Bone Physiology And Pathology
Funder
National Health and Medical Research Council
Funding Amount
$731,372.00
Summary
This project seeks to determine whether it is possible to prevent bone loss associated with osteoporosis and inflammatory bowel disease by blocking interleukin 6. Two different methods of blockade will be tested, with the hope that one of these methods will have less side effects.
The Molecular Basis By Which The Interleukin-6 Cytokine Promotes Emphysema
Funder
National Health and Medical Research Council
Funding Amount
$659,457.00
Summary
Interleukin 6 (IL-6) is a potent immuno-modulatory cytokine that is commonly elevated in emphysema, the 5th leading cause of death in Australia. To understand the role of IL-6 in emphysema, we aim to demonstrate here by using a unique mouse model for IL-6-driven emphysema and clinical biopsies from emphysema patients, that IL-6 uses an alternative signalling mechanism in emphysema termed trans-signalling. Therefore this project could provide novel therapeutic targets for emphysema.
Novel Role Of Inflammasomes In The Molecular Pathogenesis Of Emphysema
Funder
National Health and Medical Research Council
Funding Amount
$764,462.00
Summary
Emphysema is a chronic lung disease that is caused by dysregulation of the immune system, leading to inflammation and destruction of lung tissue. Although emphysema is associated with cigarette smoking, the key components of the immune system which promote emphysema remain ill-defined. Using elaborate mouse models for emphysema, together with biopsies from emphysema patients, our aim is to reveal the role of a protein complex in the immune system called the inflammasome in driving emphysema.
Validation Of Stat3 As A Therapeutic Target In Diseases Arising From Its Inappropriate Activation By Gp130 Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$674,142.00
Summary
Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach lining cells. We will employ a number of strategies to establish molecularly the exte ....Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach lining cells. We will employ a number of strategies to establish molecularly the extent to which this mouse model is informative for gastric cancer inhuman. In aprticular we will identify the genes that are involved in the progression of the disease. One important focus of the project is to see whether or not the moelcule (called Stat3) whose aberrant activation triggers the disease in the mouse could provide a future pharmacological target for intervention with the disease. Similarly with expertise of CIB, we will investigate with novel proteomics techniques whther we can identify a protein in the serum of these mice, which could give us aclue of whether or not the mouse ahs already developed disease. Such a protein could be of potentail diagnostic importance in the future to screen human for gastric cancer which in its eraly stages is usually without any clinical symptoms. In a related Aim we will find out the gene that can genetically cooperate with Stat3 and that is required to enable survival of newborn mice. It may well turn out mOur proposal combines the expertise of the two investigators in signal transduction and that this gene may be an important determinant to ensure that Stat3 triggers physiological rather than pathological responses in many differnet organs.Read moreRead less
Is The Role Of IL6 In Metabolism Dependent On Its Cellular Origin?
Funder
National Health and Medical Research Council
Funding Amount
$714,061.00
Summary
Interleukin-6 is a protein secreted from many cells in the body. For over 10 years, a great deal of research has been undertaken to determine if this protein is "good" or "bad" for patients suffering from type 2 diabetes. We have evidence that IL-6 is both good and bad depending upon which cell produces it. We intend to fully explore this notion. This is most important to clarify the confusion amongst the field and because drugs that target the IL-6 receptor complex are in clinical development f ....Interleukin-6 is a protein secreted from many cells in the body. For over 10 years, a great deal of research has been undertaken to determine if this protein is "good" or "bad" for patients suffering from type 2 diabetes. We have evidence that IL-6 is both good and bad depending upon which cell produces it. We intend to fully explore this notion. This is most important to clarify the confusion amongst the field and because drugs that target the IL-6 receptor complex are in clinical development for type 2 diabetes.Read moreRead less