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 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
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
Neurodegeneration In The Ageing Brain: How The Pathways Leading To Aggregated Protein Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$12,322,838.00
Summary
The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program ha ....The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program has identified several diagnostic and therapeutic avenues which are now being developed by the Pharmaceutical and Biotechnology industries. Much more research is still required for maximizing the chances of success using these approaches.Read moreRead less
Molecular Mechanisms Of Cardiac Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$10,053,131.00
Summary
Adult-onset heart disease remains the leading cause of death and disability in our society, with almost 2 million Australians affected. Furthermore, structural heart malformations are the most common type of abnormality at birth and the leading cause of deaths in infants dying from non-infectious causes. Many of these problems are due to defects in the development, repair and-or function of heart muscle cells or cardiomyocytes. Thus, we propose to understand, in fine detail, cardiomyocyte as wel ....Adult-onset heart disease remains the leading cause of death and disability in our society, with almost 2 million Australians affected. Furthermore, structural heart malformations are the most common type of abnormality at birth and the leading cause of deaths in infants dying from non-infectious causes. Many of these problems are due to defects in the development, repair and-or function of heart muscle cells or cardiomyocytes. Thus, we propose to understand, in fine detail, cardiomyocyte as well as integrated heart development, biology, physiology and function as a prerequisite for the development of major advances in the prevention and treatment of these disorders.Read moreRead less
Nerodegeneration In The Aging Brain: How The Pathways Leading To Aggregating Protein Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$15,050,508.00
Summary
The Neurodegeneration Program is discovering the basic pathways that cause Alzheimer’s disease and related diseases of the aging brain; from these discoveries the team are finding new methods for early diagnosis and therapeutic interventions which will allow them to determine whether it is possible to delay the onset or improve the way in which the brain copes with these diseases
The Biology And Therapeutic Manipulation Of Lymphatic Vessels In Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,688,743.00
Summary
This proposal is for an established team of researchers and clinicians to explore the molecular control of the lymphatic system. This network of lymphatic vessels, located in organs throughout the body, is critical for regulation of tissue fluid and immune function. This program will explore the molecules which control the function of lymphatic vessels and their interactions with other cells in the body. It will greatly enhance our understanding of the lymphatic vessels and identify molecular ta ....This proposal is for an established team of researchers and clinicians to explore the molecular control of the lymphatic system. This network of lymphatic vessels, located in organs throughout the body, is critical for regulation of tissue fluid and immune function. This program will explore the molecules which control the function of lymphatic vessels and their interactions with other cells in the body. It will greatly enhance our understanding of the lymphatic vessels and identify molecular targets for medicines designed to treat cancer, cardiovascular disease and lymphoedema.Read moreRead less
Heart Failure And Its Antecedents: Pathophysiology, Prevention And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$9,061,084.00
Summary
Heart failure is mainly a result of coronary artery disease. It is a major cause of disability and mortality in Australia and is projected to increase markedly over the next two decades. This program brings together clinical and basic science expertise to address aspects of the prevention and control of coronary disease and heart failure. The outcomes that will arise will provide a better understanding of the mechanisms involved in the progression from stable heart disease to failure.