Type 1 diabetes (T1D) is a major chronic disease affecting over 100,000 Australians. Its treatment and complications impose a significant burden on affected individuals and their families and on the health system. T1D occurs when the immune system attacks insulin-producing cells in the islet cells of the pancreas. The team has developed ways to identify at-risk people, defined immune and genetic causes of T1D and is undertaking prevention trials and Australia's first islet transplant program. Th ....Type 1 diabetes (T1D) is a major chronic disease affecting over 100,000 Australians. Its treatment and complications impose a significant burden on affected individuals and their families and on the health system. T1D occurs when the immune system attacks insulin-producing cells in the islet cells of the pancreas. The team has developed ways to identify at-risk people, defined immune and genetic causes of T1D and is undertaking prevention trials and Australia's first islet transplant program. Their multidisciplinary research is taking us closer to the prevention and cure of T1D.Read moreRead less
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
Molecular Mechanisms In The Regulation Of Allergy And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$4,977,215.00
Summary
To understand the fundamental cellular and molecular processes that underpin the development of allergic disorders, viral infections of the respiratory tract and chronic inflammatory diseases of the lung. There is particular interest in the role of immune cells, such T cells and granulocytes in these disorders, and in the processes that control their function. Understanding these processes will provide new insights into the immune system's role in health and disease, and help develop better ther ....To understand the fundamental cellular and molecular processes that underpin the development of allergic disorders, viral infections of the respiratory tract and chronic inflammatory diseases of the lung. There is particular interest in the role of immune cells, such T cells and granulocytes in these disorders, and in the processes that control their function. Understanding these processes will provide new insights into the immune system's role in health and disease, and help develop better therapies to treat inflammatory disorders.Read moreRead less
Atherosclerosis: Lipoproteins, Cell Biology And Vascular Physiology
Funder
National Health and Medical Research Council
Funding Amount
$10,461,682.00
Summary
The world is confronting a major new epidemic of premature heart disease that is being driven by a global increase in obesity. There are several factors that contribute to the increased risk of heart disease in overweight and obese people. One is a low blood level of the “good” HDL cholesterol that normally protects against heart disease. Another relates to a decreased ability to remove cholesterol from the walls of arteries where it builds up to cause heart disease. A third is the fact that obe ....The world is confronting a major new epidemic of premature heart disease that is being driven by a global increase in obesity. There are several factors that contribute to the increased risk of heart disease in overweight and obese people. One is a low blood level of the “good” HDL cholesterol that normally protects against heart disease. Another relates to a decreased ability to remove cholesterol from the walls of arteries where it builds up to cause heart disease. A third is the fact that obesity is associated with a state of chronic inflammation of the blood vessels. This inflammation not only accelerates the development of heart disease but also makes people who have cholesterol accumulated in their arteries more likely to actually have a heart attack. And a fourth is the fact that the lining of blood vessels does not function normally in overweight and obese people. This loss of normal function is a very early sign of future heart disease. These factors are closely inter-related, with the “good” HDL playing a central role in removing cholesterol from arteries, inhibiting arterial inflammation and promoting normal function and repair of the lining of blood vessels. HDL is complex, consisting of a mixture of several subpopulations of particles that vary in shape, size and composition. Furthermore, these HDL subpopulations are continually remodelled as they circulate in blood in reactions promoted by a number of blood factors that change their size and composition. A major component of the research to be conducted in this program relates to understanding how the HDL subpopulations in human blood are regulated and how they protect against heart disease. The applicants have already made major contributions to understanding the functions of the “good” HDLs, how they take cholesterol out of cells in the artery wall, how they inhibit inflammation of the arteries and how they improve the function of the artery lining. We propose to extend these studies to establish how these protective functions can be enhanced, to find out which of the HDL subpopulations are most protective, and to identify how to increase the most protective HDLs in people at risk of heart disease.Read moreRead less
THE INTERFACE BETWEEN INNATE AND ADAPTIVE IMMUNITY
Funder
National Health and Medical Research Council
Funding Amount
$4,905,420.00
Summary
Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in t ....Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in the laboratory with clinical investigation and analysis of human tissue. Understanding these processes will translate into better treatments for patients suffering from life-threatening allergy and asthma.Read moreRead less
Improved Respiratory Support And Outcomes For Very Preterm Babies
Funder
National Health and Medical Research Council
Funding Amount
$9,185,907.00
Summary
Premature babies are born with lungs that are not developed enough to sustain their breathing needs after birth. As a result, they need intensive care which is the most costly and challenging problem in newborn medicine as these infants can suffer life-long diseases because of their early birth. This programs study will help to understand the causes of lung disease in premature babies and develop better ways of caring for them to improve their chances of survival without ongoing illness and disa ....Premature babies are born with lungs that are not developed enough to sustain their breathing needs after birth. As a result, they need intensive care which is the most costly and challenging problem in newborn medicine as these infants can suffer life-long diseases because of their early birth. This programs study will help to understand the causes of lung disease in premature babies and develop better ways of caring for them to improve their chances of survival without ongoing illness and disabilityRead 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