The liver is an important organ in terms of immune responses. Owing to its exposure to many antigens, it is required to maintain a form of immune tolerance. This ensures that overt immune responses which would damage the liver do not occur. One means by which tolerance occurs is through silencing killer cells through the regulation of molecules of Major Histocompatibility Complex (MHC). This project will explore the role of a soluble form of MHC which is expressed only in the liver.
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$14,927,045.00
Summary
This program focuses on understanding the development of immunity during infection or inflammatory diseases using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune or inflammatory diseases.
A Structural Investigation Into The Adaptive Immune Response To A Persistent And Ubiquitous Human Virus
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
This proposal is focussed on understanding the precise shape of proteins that control the immune response to Epstein Barr Virus. EBV is an ubiquitous human pathogen that has been linked to a number of cancers. This research proposal will further our understanding of the immune response to EBV, which will lay the foundations for developing therapeutics against this disease.
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$15,780,848.00
Summary
This program focuses on understanding the development of immune response to viruses and other infectious agents using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune diseases like diabetes.
Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.
Targeting CD40L(CD154) On Dendritic Cells For CD8 T Cell-mediated Immunity And Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Killer T cells fight infection but also participate in transplant rejection. Activation of killer T cells often requires helper T cells. However, in the absence of helper cells, we have found an alternative pathway by which killer cells can be activated. We will explore this new pathway in enhancing vaccine responses and in modulating transoplant rejection.
Structural And Functional Studies Of T-cell Mediated Recognition Of Microbial Lipids Presented By CD1c
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The CD1c molecule plays an important role in the immune system by presenting lipid-based antigen of pathogens to the surface of an antigen presenting cell (APC) that is infected by the pathogen. Once a T cell receptor (TCR), which is expressed on the surface of a Killer T cell, recognises CD1c presenting pathogenic lipid, any infected cells will be destroyed. My research will look at the molecular mechanism of T cell recognising tuberculosis related lipids that is presented by CD1c.
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$15,738,750.00
Summary
The early events in immunity require various molecular interactions. We will examine the structural and biophysical basis for some of these interactions, including those associated with transplant rejection and autoimmunity. We will explore the impact of variation in immune response genes on immune evasion and disease susceptibility. Our basic research will determine the mechanisms by which the immune system discriminates between different self and micro-organism associated determinants. We will ....The early events in immunity require various molecular interactions. We will examine the structural and biophysical basis for some of these interactions, including those associated with transplant rejection and autoimmunity. We will explore the impact of variation in immune response genes on immune evasion and disease susceptibility. Our basic research will determine the mechanisms by which the immune system discriminates between different self and micro-organism associated determinants. We will address the structural and biochemical basis for operation of an immune molecule called tapasin and unravel the basis for how some viruses escape the function of this molecule, thus allowing their immune evasion. We will also explore the use of modified small proteins called peptides in a humanized model of gluten hypersensitivity resembling that of Celiac disease. The molecular basis of the natural human immune system's capacity to recognise and reject grafts will be examined. This complements work aimed at improving the prediction of clinical graft rejection in transplantation. Dendritic cells play a central role in immunity, responsible for capturing material, whether from micro-organisms or self tissues, and presenting it to cells of the immune system. Our program will study the development and immunological function of the different dendritic cell subtypes. We will determine the relative contribution of each to the maintenance of immune tolerance and to the induction of immunity to several pathogens, including herpes simplex virus and malaria. Novel dendritic cell surface molecules that we have discovered will be tested for their ability to enhance the effectiveness of vaccines. Overall, this program utilises a broad array of immunological techniques designed to dissect the development and function of various immune system cell types and determine the structure-function relationships between important cell surface molecules involved in immunity.Read moreRead less