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
Developmental Aspects Of Respiratory Inflammation, Allergy And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$7,169,609.00
Summary
Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longit ....Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longitudinal studies in cohorts of children recruited before birth. Having the ability to study children as they grow and develop conditions such as allergies and asthma allows us to understand why these conditions occur and allow us to predict which children are likely to develop them. Our research Program also has a solid focus on Translational Research, in which we will use the findings from our basic science studies to develop and test new methods of preventing and of treating asthma. These studies will include new methods for preventing the development of allergies, preventing the damage done to the lungs by severe viral respiratory infections in early life and better methods of treating established allergic asthma by improving immunotherapy techniques. By its very nature, primary prevention of disease in young children is controversial and raises some interesting questions. As part of this Program we intend to initiate consultation and debate in public, academic, regulatory and industry circles. An important role for our Program is shifting the current emphasis away from treatment of established disease towards preventing disease occurring. This is the best way to decrease the health, social and economic burden of chronic diseases such as asthma.Read moreRead less
Novel Strategies For Improving Respiratory Support And Outcomes For Very Preterm Babies
Funder
National Health and Medical Research Council
Funding Amount
$8,381,820.00
Summary
Very premature birth is the commonest cause of illness and death in newborn babies, making it one of the most serious and costly issues in perinatal medicine. The major problem suffered by very premature babies is lung immaturity and its associated harmful effects on brain development. Most very premature babies require resuscitation followed by ventilatory support,often for several weeks. This is extremely expensive and places an enormous financial burden on health care systems. Furthermore, it ....Very premature birth is the commonest cause of illness and death in newborn babies, making it one of the most serious and costly issues in perinatal medicine. The major problem suffered by very premature babies is lung immaturity and its associated harmful effects on brain development. Most very premature babies require resuscitation followed by ventilatory support,often for several weeks. This is extremely expensive and places an enormous financial burden on health care systems. Furthermore, it increases the risks of respiratory illnesses, including bronchopulmonary dysplasia and chronic lung disease which can impair breathing and increase susceptibility to respiratory disease such as asthma later in life. The overall aim of this program is to improve outcomes for very premature babies, including less lung injury, better respiratory health and shorter stays in hospitals. In order to reduce the health burden caused by very premature birth on the community we need to know more about how it alters the normal development of the lungs in the newborn period and into later life. In particular, we need to understand the cellular and molecular processes involved in lung development so that we can identify gene networks and developmental processes that are disrupted by severe premature birth. Such knowledge is necessary to provide a more rational, scientific basis for managing and treating the alterations in lung structure and function caused by premature birth. We also need to develop better ways of resuscitating and ventilating these infants so that lung injury is minimized.The research team is led by two neonatologists and three biomedical research scientists with a proven record of effective collaboration. This team is internationally unique in that it includes practicing neonatologists, respiratory physiologists and molecular biologists who have collaborated together productively and are regarded as world leaders in their respective fields. New talents have been brought into the team to provide expertise in pulmonary stem cell biology, the design of novel steroid drugs, and clinical follow-up. Together, this team has the potential (a) to greatly enhance the understanding of the impact of very premature birth on the developing lung, (b) to improve resuscitation and ventilation techniques, and (c) to translate the new knowledge into clinical practice to improve the outcome for prematurely born babies. Using well characterized animal models we will determine gene networks involved in fetal lung development and how these are altered by premature birth. The successful transition from fetal to postnatal life is critical for survival at birth but more information is needed. Using newborn lambs and rabbits, we will trial novel strategies for enhancing the transformation of the immaturelung into an effective gas exchange organ at birth. New data on lung aeratioRead moreRead less
This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to dev ....This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to develop more effective and selective treatments ofchronic inflammatory disease in humans.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
Molecular Regulation Of Blood Cell Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$18,333,174.00
Summary
The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinica ....The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinical strategies for fighting these lethal diseases. This program is conducted by a large, established team of investigators that have made world-class contributions to understanding blood cell formation and function for more than 30 years. Their work established the modern era of molecular haematology via discovery and analysis of blood cell hormones (colony-stimulating factors or CSFs), their receptors and intracellular mediators, which resulted in development of treatments for millions of cancer patients. The program is a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes involving collaborations with clinical medicine and the pharmaceutical industry. Research will focus on meshing novel genetic approaches in mice with translation studies in humans to identify new validated targets for therapeutic intervention in blood cell diseases, as well as building on the team s expertise in cytokine action with emphasis on the actions of the suppressor of cytokine signalling (SOCS) molecules, a key family of proteins that controls cytokine actions.Read moreRead less
Molecular And Cellular Studies Of The Adaptive Immune Response In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$16,509,154.00
Summary
Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the ....Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the-art technologies, including genetically modified mice, gene microarrays, monoclonal antibodies, and flow cytometry. We have brought together Australia's leading immunologists with complimentary expertise and research interests in specific areas of immunology including cytokines, cell migration, inflammatory diseases, autoimmunity and cell-cell interactions. One aspect of the application is to understand the genetic and molecular basis of immunological diseases. However we also wish to move on from an understanding to treatment of immunological diseases through the development of novel therapeutics. We will form collaborations with biotech and pharmaceutical companies (including our own spin off companies) to advance important new therapeutics for autoimmune and allergic diseases. These conditions represent a significant health burden to Australia.Read moreRead less
Immunological Therapies For Cancer, Chronic Infection And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$10,891,788.00
Summary
The team comprises five leading scientists with a history of successful investigation into the role of the immune system in cancers, chronic viral infections, and autoimmune diseases. There is a large unmet need for effective solutions with fewer side effects in these diseases which cause a high disease burden in our society. In this program, we particularly seek to develop novel vaccines for chronic infections and autoimmune diseases, and to improve the safety of bone marrow transplantation.
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