I am a viral immunologist studying the requirements for an effective host response to viral infection. I am also investigating the potential for the development of efficacious vaccines to protect against infection and ways of intervening in the disease pr
Defining The Molecular Effectors And Regulators Of Anti-viral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
In humans, cytomegalovirus infection can cause severe disease and may even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The majority of healthy individuals however can clear the infection with minimal disease. The ability of cytomegalovirus to cause disease is increased in the absence of effective immune responses which would normally clear the virus before illness occur ....In humans, cytomegalovirus infection can cause severe disease and may even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The majority of healthy individuals however can clear the infection with minimal disease. The ability of cytomegalovirus to cause disease is increased in the absence of effective immune responses which would normally clear the virus before illness occurs. Understanding the role of specific mediators of anti-viral immune responses is therefore of paramount importance in establishing the guidelines for the design of more effective anti-viral therapies. The mouse model of cytomegalovirus infection provides a unique system to dissect the roles of specific components of the immune response during the course of viral infection. Our previous studies have shown that anti-viral immune responses are complex and involve a multitude of players. The central aim of the work in the current proposal is to establish the precise contribution of specific molecular effectors and regulators of anti-viral immune responses and define their relevance during the different stages of viral infection. Hence, the results of these studies will be relevant to understanding the pathogenesis of cytomegalovirus infection in humans and more importantly will provide critical insights into the rational design of improved antiviral drugs and vaccines. Since the molecules and cells under investigation are also known to play a crucial role in immune responses that control tumour growth and transplant survival, the proposed studies will provide valuable insight towards the development of new therapies for pathologies associated not only with cytomegalovirus infection, but also with the conditions named above.Read moreRead less
Biology Of The Novel C-type Lectin Receptor DCL-1 In Innate And Adaptive Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
The innate immune system is the first line of defense in protecting the body from infection. Phagocytic (meaning eating) white blood cells, which include dendritic cells and macrophages are equipped with cell surface proteins These bind the many types of microbes that cause infection, allowing the phagocytes to destroy them (innate immune response). Furthermore, dendritic cells and macrophages have mechanisms to activate additional specific responses (adaptive immune response) mediated by lympho ....The innate immune system is the first line of defense in protecting the body from infection. Phagocytic (meaning eating) white blood cells, which include dendritic cells and macrophages are equipped with cell surface proteins These bind the many types of microbes that cause infection, allowing the phagocytes to destroy them (innate immune response). Furthermore, dendritic cells and macrophages have mechanisms to activate additional specific responses (adaptive immune response) mediated by lymphocytes (T and B cells). We have discovered a cell surface protein, termed DCL-1, which may play a role in uptake of microbes by phagocytes and activation of innate and adaptive immune responses. This project will examine the mechanisms whereby DCL-1 mediates these immune responses. Understanding the mechanism may allow us to exploit DCL-1 for tumor immunotherapy.Read moreRead less
Chromatin Remodelling And Transcriptional Regulation Of CD8 T Cell Effector Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
A major role for cytotoxic, or killer, T cells is the recognition and removal of virus infected or tumor cells from a host. Upon recognition of a target host cell, killer T cells deliver a package of proteins, termed granzymes, that mediate the removal of these virus infected and tumor cells. Naive killer T cells need to be activated to start producing these effector molecules. This proposal plans to examine the factors that regulate both induction and maintanence of cell specific expression of ....A major role for cytotoxic, or killer, T cells is the recognition and removal of virus infected or tumor cells from a host. Upon recognition of a target host cell, killer T cells deliver a package of proteins, termed granzymes, that mediate the removal of these virus infected and tumor cells. Naive killer T cells need to be activated to start producing these effector molecules. This proposal plans to examine the factors that regulate both induction and maintanence of cell specific expression of these effector molecules. We plan to identify the molecular events that occur within a cells genome to turn on granzyme gene expression and how these factors influence subsequent killer T cell function. The conclusions from these studies will enable us to determine why some killer T cell responses are not effective and what can be done to improve killer T cell function. This has implications for the development of novel vaccine strategies designed to induce immunity against both viral and tumour challenges.Read moreRead less