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
The Molecular Basis Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$16,230,996.00
Summary
Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as ....Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as novel drugs. These are urgently needed to reduce death and illness due to bacterial infectious diseases in the 21st century. 11Read 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
While current influenza vaccines blunt winter epidemics, they must be updated frequently to keep up with virus mutation and they do not protect against pandemics caused by new flu viruses (such as bird flu). This program will define how flu virus interacts with the immune system to generate immunity mediated particularly by “killer” T cells. We will use this knowledge to develop and evaluate vaccines that induce long-lasting T-cell immunity that can protect against both seasonal and pandemic flu ....While current influenza vaccines blunt winter epidemics, they must be updated frequently to keep up with virus mutation and they do not protect against pandemics caused by new flu viruses (such as bird flu). This program will define how flu virus interacts with the immune system to generate immunity mediated particularly by “killer” T cells. We will use this knowledge to develop and evaluate vaccines that induce long-lasting T-cell immunity that can protect against both seasonal and pandemic flu.Read moreRead less
Determinants Of Child Health And Development: Populations, Partnerships, Pathways And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$8,214,333.00
Summary
There are considerable challenges to the study of complex health and developmental problems in children and young people. Despite increasing prosperity in Australia, many of these problems are not abating and some appear to be increasing. These include low birthweight, behavioural and mental health problems, autism, obesity and, in Indigenous children, infections. This Program proposes investigating these problems with a view to prevention, thus meeting the national research priority of Promotin ....There are considerable challenges to the study of complex health and developmental problems in children and young people. Despite increasing prosperity in Australia, many of these problems are not abating and some appear to be increasing. These include low birthweight, behavioural and mental health problems, autism, obesity and, in Indigenous children, infections. This Program proposes investigating these problems with a view to prevention, thus meeting the national research priority of Promoting and Maintaining Good Health, particularly _a healthy start to life� and _preventive health care�. The Program is unique in that it brings together a multi-disciplinary team of researchers of international repute to investigate these complex issues. The research team comprises epidemiologists, clinicians, developmental psychologists, biostatisticians, sociologists and other social scientists. This team has a proven track record in producing research outcomes that have translated into innovative health policy and practice in areas as diverse as: - the use of folic acid in spina bifida prevention - understanding cerebral palsies - suicide prevention and mental health in children and young people - Aboriginal child health and development - intellectual disabilities including Rett syndrome and autism - in vitro fertilisation and birth defects. The factors influencing how children develop into young adults include genetic inheritance, nutrition and growth, and family, socioeconomic and environmental conditions. This work demands new ways of measuring and analysing these factors in populations of children and their families. Western Australia is one of only three sites in the world to have comprehensive linked health data on the whole of its population of children and their families. This Program comprises five overlapping themes of research planned around these unique population databases. The five themes are: - social, economic and psychological influences on child health and development - many paths to poor health are linked to social disadvantage. Examining these issues may explain why some childhood conditions are worsening or not improving - pathways to wellbeing, resilience and developmental disorders, including intellectual disability, autism, birth defects and cerebral palsy - nutrition and growth, particularly as it relates to low birthweight, childhood obesity and mental health - infectious disease, its causes and its influence on lifelong health problems and disabilities - Aboriginal health _ whilst spanning each of the research themes above, it presents its own unique challenges and requires it�s own unique solutions. This Program will investigate how children develop into young adults and will examine the influence of their families, nutrition and growth and socioeconomic and environmental conditions. It will develop new ways of measuring and analysRead 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
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