A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
Immunomodulatory Vaccines In The Treatment Of Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$678,899.00
Summary
Peanut allergy is the most common cause of food-induced anaphylactic reactions in Australia and is a major burden to our healthcare system. Current clinical practice advice dietary avoidance to prevent fatal anaphylactic responses. We propose the use of an immunomodulatory vaccine to re-write the immune response to peanut antigens, from an allergic to a tolerant phenotype. This study will provide novel insights into rational approaches for manipulating immune memory to food allergens.
The Role Of Novel G-Protein Coupled Receptors In Immunity And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$69,684.00
Summary
Recent advances in molecular biology techniques have resulted in the identification of many novel GPCRs. Novel GPCRs expressed selectively on immune cells display a potential target for novel therapies for inflammatory diseases such as Asthma and Rheumatoid arthritis. This project aims to define the activity and significance of a novel group of GPCRs, the GPR40 family. Outcomes of this project will be further understanding of immune cell development and inflammatory disease development.
Analysis Of Viral And Cellular Gene Expression During Human Cytomegalovirus Latent Infection Of Hematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
Summary
Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body a ....Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. This project has three major components. Firstly, we aim to continue studies which are defining what viral genes are active (ie expressed) during latent infection. Identification of these genes and determination of how they function may have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during latency and reactivation. The study of viral and cellular gene expression during latency may contribute to the development of drugs which interfere with the viruses ability to become latent or reactivate. Thirdly, we have preliminary results which suggest that latent HCMV may actively avoid detection by the immune system. In this project we also aim to determine the mechanism by which the virus interferes with the expression of molecules which are an essential component of our immune system.Read moreRead less
Special Research Initiatives - Grant ID: SR140100001
Funder
Australian Research Council
Funding Amount
$35,000,000.00
Summary
The Juvenile Diabetes Research Foundation Australian Type 1 Diabetes Research Network and Program. This Proposal continues the development of the initial Type 1 Diabetes Clinical Research Network (CRN), launched by JDRF in June 2011 with a $5m grant from the Australian Government.
The principal goal of the CRN is to positively impact the life of people with T1D in Australia through the support and promotion of clinical research. A further electoral commitment of $35m over 5 years will enable f ....The Juvenile Diabetes Research Foundation Australian Type 1 Diabetes Research Network and Program. This Proposal continues the development of the initial Type 1 Diabetes Clinical Research Network (CRN), launched by JDRF in June 2011 with a $5m grant from the Australian Government.
The principal goal of the CRN is to positively impact the life of people with T1D in Australia through the support and promotion of clinical research. A further electoral commitment of $35m over 5 years will enable further progress towards finding a cure for T1D, including delivering better and faster access to new therapies and treatments that can help prevent and manage the disease.
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Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the ....Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the way we think about the clonal selection of lymphocytes, the fundamental theory underlying our understanding of the immune system.Read moreRead less
CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the ....CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the age that an individual first encounters the infection. Our project will identify critical periods in life that direct T cell programming to subsequent protective or destructive responses, providing new insights into the developing immune system that may be exploited to treat disease or develop vaccines.Read moreRead less
Analysing the protective role of platelets during malaria infection. Platelets protect the host during malarial infection. This project aims to study how platelets kill the malaria parasite by investigating the role of host molecules and their potential as novel antimalarial agents. The role of platelets in the pathogenesis of cerebral malaria syndrome will also be investigated.
Mechanism of action of an anti-inflammatory compound which targets alternatively activated macrophages. The project will study the mechanism by which a novel anti-inflammatory compound, developed by our commercial partner, suppresses the activity of a population of cells known as alternatively activated macrophages. These cells play a key role in driving allergic inflammation, including the inflammation associated with asthma.
Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will gene ....Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will generate significant economic spin-offs to the Australian biotechnology industry and will further relationships and training between research and development.Read moreRead less