Methylation Sensitive Genes And The Transition To Allergic Disease: A Twin Study
Funder
National Health and Medical Research Council
Funding Amount
$493,843.00
Summary
Australia has amongst the highest reported prevalence allergic conditions (including asthma) in the world. Despite this, little is known about how these conditions arise. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of a unique collection of identical twins where one of a pair is sensitive to house dust mite, with cutting edge genomics, to characterise the pathways leading to allergy in ....Australia has amongst the highest reported prevalence allergic conditions (including asthma) in the world. Despite this, little is known about how these conditions arise. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of a unique collection of identical twins where one of a pair is sensitive to house dust mite, with cutting edge genomics, to characterise the pathways leading to allergy in children.Read moreRead less
Neutrophil Regulation Of Early Adaptive Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$613,273.00
Summary
The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammator ....The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammatory diseases.Read moreRead less
ANTIGEN PRESENTATION IN CEREBRAL MALARIA PATHOGENESIS: A ROLE FOR BRAIN MICROVASCULAR ENDOTHELIUM AND MICROPARTICLES
Funder
National Health and Medical Research Council
Funding Amount
$416,012.00
Summary
We want to better understand how lesions occur in the brain during cerebral malaria. We focus our attention on the cells lining the brain blood vessels, called endothelial cells. The originality of this project is to study endothelial cells as immune cells. We already showed that they carry molecules enabling them to activate T lymphocytes and trigger inflammation. Knowing the fine mechanisms by which small brain vessels become damaged will help design better treatments for neuroinflammation.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
Failure Of Donor Antigen Presentation Promotes IL-17 Dependant Chronic GVHD
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which d ....Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which drive GVHD.Read moreRead less
The Role Of Gut Resident Antigen Presenting Cells In Graft-versus-host Disease
Funder
National Health and Medical Research Council
Funding Amount
$409,909.00
Summary
Allogeneic stem cell transplantation (SCT) is curative therapy for most blood cancers, since donor immune cells can eliminate cancers which cannot be eradicated by chemotherapy. However these donor cells can also attack normal cells in a process known as graft-versus-host disease. This research aims to understand how immune responses are induced after SCT to promote cancer eradication, whilst inhibiting GVHD, thus curing more patients of cancer and maintaining a normal quality of life.
The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
Transcriptional Regulation Of Specialized Subsets Of Dendritic Cells In Control Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
Immune protection against viruses and bacteria depends on specialized cells called dendritic cells that display components of the invading organisms on their surface. There are multiple different types of dendritic cell and each population plays a specialized role in defending the body against infection. Our work will provide the framework for directly targeting these cells for novel vaccines to re-program the immune system for clinical conditions such as cancer, allergy and autoimmunity.
A Novel Role For The IL-2 Pathway In Type-1-diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$548,548.00
Summary
Genes encoding IL-2 and its receptor are strongly linked to susceptibility to multiple autoimmune diseases, including type-1-diabetes. Despite the importance of this pathway in the immune system, it is not yet understood how the associated genes affect disease. In this study, a novel function for IL-2 expression by dendritic cells in normal self-tolerance is investigated. The impacts of dendritic cell produced IL-2 expression and linkage to autoimmunity will be elucidated in both mouse and man.
Reversing Autoimmune Diabetes By Controlling Pathogenic Effector T-cells
Funder
National Health and Medical Research Council
Funding Amount
$408,662.00
Summary
Type 1 diabetes (T1D) results from misdirected immune responses that destroy insulin-producing pancreatic cells. The ultimate goal of therapeutic strategies is to remove or inactivate the cells that attack insulin-producing cells, while leaving other cells, for example, those required for protection from infectious diseases and tumours, unaffected. Here we propose to test a new way of turning off the inappropriate immune reaction with the goal of preventing type 1 diabetes.