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
The Translation Of Dendritic Cell Biology Into Clinical Practice
Funder
National Health and Medical Research Council
Funding Amount
$3,674,406.00
Summary
This Program combines world recognized expertise in the science of immunology and the blood system, with top Australian expertise in the practice of bone marrow transplantation and the treatment of hematological malignancies. Its vision is to study the biology of dendritic cells, which are the specialized white cells that initiate the immune response, and then, to apply this knowledge to the design and introduction of novel diagnostic and therapeutic immune strategies, to improve the survival of ....This Program combines world recognized expertise in the science of immunology and the blood system, with top Australian expertise in the practice of bone marrow transplantation and the treatment of hematological malignancies. Its vision is to study the biology of dendritic cells, which are the specialized white cells that initiate the immune response, and then, to apply this knowledge to the design and introduction of novel diagnostic and therapeutic immune strategies, to improve the survival of patients with leukaemia, lymphoma and multiple myeloma.Read moreRead less
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� c ....This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� cells that can rapidly become antibodyproducing cells should the same infection occur again in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an antibody-producing cell, by studying the genes that are known to be required for the cells to form, or to do their work. We will study animals whose immune systems are under- or over-active, to find out what part of the antibody-producing process is faulty. Using this information, we hope eventually to be able to study diseases of antibody producing cells in humans (as occur in allergy, asthma, rheumatoid arthritis and leukaemia), to be able to identify the precise cause of the problem, and to suggest a therapy. This information may also be used to improve the outcome of vaccination where an enhanced antibody response is desired.Read moreRead less
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
This established team of investigators will research into the molecular control of white blood cell formation and function, using a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes. The team will also attempt to identify new validated targets for therapeutic intervention by using both forward and reverse genetic approaches in mice coupled with complete phenotypic analyses of the blood cell system.
This Program Grant has three investigators, Professor Denis Moss, Dr Rajiv Khanna and Dr Scott Burrows, each of whom has collaborated on two previous Program Grants. The group is well known in the area of herpesvirus immunology and have published numerous scientific papers in leading medical journals. This program grant focuses on two human herpesviruses. The first is called Epstein-Barr virus which causes glandular fever and is associated with arange of human cancers. The second virus is human ....This Program Grant has three investigators, Professor Denis Moss, Dr Rajiv Khanna and Dr Scott Burrows, each of whom has collaborated on two previous Program Grants. The group is well known in the area of herpesvirus immunology and have published numerous scientific papers in leading medical journals. This program grant focuses on two human herpesviruses. The first is called Epstein-Barr virus which causes glandular fever and is associated with arange of human cancers. The second virus is human cytomegalovirus which can cause birth defects and problems in transplant patients. In this program we are investigating how the body�s immune system controls these viruses to exploit this information to develop new treatments.Read moreRead less