Disorders of sexual development (DSDs) are surprisingly common, and often result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. In this Program we will pool our expertise in human molecular genetics, mouse developmental biology and protein chemistry to identify genes important for sex determination and development of the gonads, and discover how they contribute to DSD, in order to improve clinical care to patients with DSD.
Molecular Genetics Of Sex Determination And Gonad Development
Funder
National Health and Medical Research Council
Funding Amount
$4,580,898.00
Summary
Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo ....Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo. This research program will identify genes important for sex determination and development of the gonads, find out how these genes function and interact, and discover how they contribute to cases of aberrant sexual development in humans. Australia boasts three of the foremost international researchers in sex determination. Their contributions have been fundamental to the advancement of the field, including the identification and characterization of the master testis determining gene and other genes critical for sex determination. They now propose to pool their expertise in human molecular genetics, mouse developmental biology and protein chemistry to bring spectacular advances in our knowledge of human sexual development and its associated disorders. This information will be used to bring improved clinical care to patients withdisorders of sexual development.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
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
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
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 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.
The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Unfortunately the immune system can sometimes lose specificity and attack the host resulting in autoimmune diseases such as diabetes. This research team has played a vital role in characterising the specific activities of immune cells and the associated factors. By understanding these complex processes the team aims to harness the unique therapeutic pro ....The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progression. Unfortunately the immune system can sometimes lose specificity and attack the host resulting in autoimmune diseases such as diabetes. This research team has played a vital role in characterising the specific activities of immune cells and the associated factors. By understanding these complex processes the team aims to harness the unique therapeutic properties of our own immune system and translate their findings into the clinic.Read moreRead less
Molecular Mechanisms Of Cardiac Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,213,642.00
Summary
Heart disease remains the leading cause of death in our society. Almost two million Australians suffer from the debilitating effects of heart disease and it is the leading cause of premature permanent disability in our workers. Heart defects are also the most common type of birth defect and the leading cause of deaths in infants dying from birth defects. Many of these problems can be attributed directly to defects in the development, repair and-or function of heart muscle and, at the cellular le ....Heart disease remains the leading cause of death in our society. Almost two million Australians suffer from the debilitating effects of heart disease and it is the leading cause of premature permanent disability in our workers. Heart defects are also the most common type of birth defect and the leading cause of deaths in infants dying from birth defects. Many of these problems can be attributed directly to defects in the development, repair and-or function of heart muscle and, at the cellular level, of heart muscle cells or cardiomyocytes. Understanding the cardiomyocyte as well as integrated heart development, biology, physiology and function, therefore, holds great promise for major advances in the prevention and treatment of contemporary heart diseases. This Program Grant brings together a unique team of interactive researchers with expertise in cardiovascular physiology, as well as developmental, cellular and molecular biology. The outcomes anticipated from new insights into heart biology that will result from the proposed studies, are the development of novel therapeutic approaches for the prevention and treatment of heart attacks and heart failure.Read moreRead less