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.
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.
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.
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
Identification Of Interleukin-6 Trans-signalling As A Novel Target For Therapeutic Approaches To Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$627,089.00
Summary
Interleukin-6 (IL-6) has been implicated as a causative factor in lung cancer, the most lethal cancer worldwide, albeit by unknown mechanisms. Since IL-6 is also important for immune system homeostasis, the development of anti-IL-6 therapies requires an intimate knowledge of pathological versus physiological IL-6 signalling pathways. This project aims for the first time to define an alternative IL-6 signalling pathway, termed “trans signalling”, in the molecular pathogenesis of lung cancer.
The Interplay Between IL-6 And GVHD On Anti-viral And Anti-leukaemic Immunity
Funder
National Health and Medical Research Council
Funding Amount
$489,376.00
Summary
Bone marrow transplantation can cure leukaemia but infection, graft-versus-host disease (GVHD) and leukaemia relapse remain challenging problems. We recently completed an early phase clinical study on GVHD prevention using interleukin-6 blockade. Interestingly, the rate of virus reactivation was also lower. This project will use a newly developed mouse model and stored clinical samples to understand the underlying mechanism and whether it also has an impact on anti-leukaemic immunity.