Adult Consequences Of Childhood Exposure To Psychological Trauma
Funder
National Health and Medical Research Council
Funding Amount
$292,530.00
Summary
The importance of childhood experience to adult adjustment (DOES THIS MAKE SENSE) is an issue of general public health interest. In particular, in the area of personality development, there are a number of theories concerning the importance of childhood experience and developmental stresses on later personality, development, psychological functioning and physical health. More recently there has been debate on the accuracy with which adults areable to remember traumatic experiences in childhood. ....The importance of childhood experience to adult adjustment (DOES THIS MAKE SENSE) is an issue of general public health interest. In particular, in the area of personality development, there are a number of theories concerning the importance of childhood experience and developmental stresses on later personality, development, psychological functioning and physical health. More recently there has been debate on the accuracy with which adults areable to remember traumatic experiences in childhood. This study will follow a group of 808 primary school children who were exposed to the 1983 Ash Wednesday bushfires in SOuth Australia. They were involved in a study which examined them two months, eight months and twenty six months after the disaster. This rich descriptive set of information about these children and their families forms an objective data base against which their adult recall of the experience can be judged. The symptoms of these children were also documented at the time as was their disaster exposure. The impact of this one event, in the context of the other developmental influences will be examined as determinants of their adjustment in adult life. Finally, there has been an increasing interest in the way that previous traumatic exposure influences the nature of the hormonal response to stress. Using a test of functioning of the cortisol system, the stress response of this population will be compared with a control population who were also studied at the time of the original disaster.Read moreRead less
The Transcriptional Regulation Of Lymphocyte And Dendritic Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$596,051.00
Summary
The distinct cell types of the blood, such as red and white blood cells, are produced in the bone marrow from a rare stem cell. An important characteristic of the stem cell is its ability to balance the need to proliferate and produce the distinct cell types (termed differentiation) and the need to maintain an adequate number of stem cells in their primitive state (termed self-renewal). The outcome of this balance is the production, throughout life, of an astounding number of cells that are requ ....The distinct cell types of the blood, such as red and white blood cells, are produced in the bone marrow from a rare stem cell. An important characteristic of the stem cell is its ability to balance the need to proliferate and produce the distinct cell types (termed differentiation) and the need to maintain an adequate number of stem cells in their primitive state (termed self-renewal). The outcome of this balance is the production, throughout life, of an astounding number of cells that are required to replace those lost each day. This feat is controlled by a handful of important master-regulatory genes that act in a hierarchy to promote the differentiation process. This tightly controlled and multi-step regulation is essential, as failure to coordinate blood cell production is the underlying cause of many blood cell cancers such as leukaemia as well as immune deficiency and anaemia. This research aims to understand how these master-regulators function in isolation and together in producing the white blood cells that are required for our immune response to microbes, vaccination and to prevent cancer.Read moreRead less
Transcriptional Control Of Blood Vessel Development By Sox18
Funder
National Health and Medical Research Council
Funding Amount
$468,564.00
Summary
Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body. Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of ....Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body. Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. As a result of our collaborative research efforts, we have discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or behaviour of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) through pharmaceutical intervention.Read moreRead less
The Role Of Sox8 In Sex Determination And Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
We have discovered a new gene called Sox8. This gene is very closely related to another gene, Sox9, that is known to be a critical factor in determining whether an embryo develops as a male or female by specifying whether the embryo makes testes or ovaries. We have found that Sox8, like Sox9, is active in the cell type in fetal testes known to be important for the development of maleness, at around the time when the male-female decision is being made. We therefore believe that Sox8 is an importa ....We have discovered a new gene called Sox8. This gene is very closely related to another gene, Sox9, that is known to be a critical factor in determining whether an embryo develops as a male or female by specifying whether the embryo makes testes or ovaries. We have found that Sox8, like Sox9, is active in the cell type in fetal testes known to be important for the development of maleness, at around the time when the male-female decision is being made. We therefore believe that Sox8 is an important part of the genetic chain of events leading to normal male development. We aim to study how Sox8 exerts its effects on male development. We have also found that in humans, Sox8 is located in a chromosomal region associated with a developmental disease syndrome characterized by mental retardation, facial defects and anomalies of male sexual development. Sox8 is active in mouse embryos in all the tissues affected by the human disease. We believe defects in SOX8 in humans are largely responsible for this disease, called ATR-16 syndrome. We will test whether patients with ATR-16 have defects involving SOX8 in their DNA in order to test this theory. In summary, we believe we have found a new human disease gene which will further our understanding of how developmental diseases arise in the embryo. In addition, this work will shed light on the process of sexual development, a significant healthcare problem in view of the fact that defects in sexual development are among the most common forms of birth defects.Read moreRead less
Control Of Blood Vessel Development By SOX Transcription Factors
Funder
National Health and Medical Research Council
Funding Amount
$495,750.00
Summary
Cardiovascular disease is Australia s greatest health problem, with an estimated 3 million Australians suffering a spectrum of conditions from hypertension through to heart failure. Improper development of blood vessels in the embryo can compromise survival of the embryo, and predispose patients to vascular disease after birth. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fu ....Cardiovascular disease is Australia s greatest health problem, with an estimated 3 million Australians suffering a spectrum of conditions from hypertension through to heart failure. Improper development of blood vessels in the embryo can compromise survival of the embryo, and predispose patients to vascular disease after birth. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. We discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or properties of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) by drug treatments.Read moreRead less
Co-ordinating The Intrinsic And Extrinsic Arms Of Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$615,286.00
Summary
The cell types of the blood, such as red and white blood cells, are produced in the bone marrow from a rare stem cell. The stem cell uses a handfull of important master-regulatory genes that act in a hierarchy to promote the blood cell differentiation process. This research aims to understand how these master-regulators function in isolation and together in producing the white blood cells that are required for our immune response to microbes, vaccination and to prevent cancer.
Trajectories Between Childhood Internalising Behaviour Problems And Adolescent Depressive Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$55,000.00
Summary
Depressive symptoms are known to escalate sharply through the adolescent years. Adolescents who experience an episode of depression are very likely to experience further mental illness as adults. Efforts to prevent depressive illness may be advanced by research delineating the factors and processes implicated in the early emergence of depressive symptoms. To advance such an understanding this project will analyse data collected, in part, through NHMRC support to Australian Temperament Project (A ....Depressive symptoms are known to escalate sharply through the adolescent years. Adolescents who experience an episode of depression are very likely to experience further mental illness as adults. Efforts to prevent depressive illness may be advanced by research delineating the factors and processes implicated in the early emergence of depressive symptoms. To advance such an understanding this project will analyse data collected, in part, through NHMRC support to Australian Temperament Project (ATP) researchers. The ATP data will be used to examine factors associated with the development and progression of depressive symptoms from childhood to adolescence. The ATP data set includes detailed longitudinal data collected from multiple sources (parents, teachers and youth) concerning child and adolescent temperament, behavioural problems, mother-child relations, health, depressive symptoms, school achievement, school adjustment, social skills, peer relationships, parenting practices, stressful life events, and sociodemographic factors. Of an original sample of 2443 enrolled in the cohort in 1983 (aged 4-8 months) a subsample of 1,350 adolescents should complete the data collection due in 2000 (age 17-18). Through the analysis of ATP data proposed in this application, models will be developed to explain the risk and resiliency processes in childhood and early adolescence influencing the development and course of adolescent depression, for different subgroups of adolescents. To achieve this objective, analyses will: 1. identify groups who have differing trajectories from childhood internalising behaviour problems to adolescent depressive symptoms; 2. compare groups to identify factors that contribute to the progression from internalising behaviour problems to depressive symptoms, while also identifying factors which appear to impede such progression and; 3. compare groups to identify factors associated with transient versus persistent depressive symptoms in adolescence.Read moreRead less
Schizophrenia is a group of brain disorders that affects approximately 1 in 100 people. The symptoms can include delusions (false beliefs), hallucinations (e.g., hearing voices), blunted emotions, poor planning ability and reduced motivation. Because these disorders often start in early adulthood, and can be chronic, schizophrenia contributes substantially to the burden of disease across the globe. The causes of schizophrenia are poorly understood, but it is clear that both genetic factors and e ....Schizophrenia is a group of brain disorders that affects approximately 1 in 100 people. The symptoms can include delusions (false beliefs), hallucinations (e.g., hearing voices), blunted emotions, poor planning ability and reduced motivation. Because these disorders often start in early adulthood, and can be chronic, schizophrenia contributes substantially to the burden of disease across the globe. The causes of schizophrenia are poorly understood, but it is clear that both genetic factors and environmental factors can contribute to the risk of developing schizophrenia. As part of an integrated program of research searching for novel environmental risk factors for schizophrenia, this application examines the impact of low prenatal vitamin D on brain development. Vitamin D is a steroid hormone mostly derived from the action of bright sunshine on the skin. Our past research (based on population studies, cell culture studies and animal experiments) have provided tantalizing clues about the impact of low prenatal vitamin D on brain development. This project will explore two important areas. We will explore mechanims by which LOW vitamin D may cause LESS programmed cell death (apoptosis). Programmed cell death is a crucial feature in brain development, and any alteration to the orderly sequence of brain development may leave the person vulnerable to adult-onset brain disorders like schizophrenia. Secondly, we will compare the behaviour and brain markers of adult rats born of mothers depleted of vitamin D versus normal mothers. Finally, we will examine the impact of vitamin D on neural tissue cultures obtained from nasal biopsy. If low prenatal vitamin D is a risk factor for schizophrenia, then it may be possible to reduce the incidence of schizophrenia by providing pregnant women with a safe and cheap vitamin tablet (similar to how folate supplements have reduced the incidence of spina bifida) .Read moreRead less
Improving Neurobehavioural Development In Preterm Infants: A Randomised Controlled Trial Of A Neonatal Intervention
Funder
National Health and Medical Research Council
Funding Amount
$680,920.00
Summary
Up to 50% of preterm infants will have one or more developmental difficulties. While medical complications are implicated in these problems, recent evidence points to the added effect of the infant's early environment. Hospitalised premature infants experience stress from necessary but painful hospital procedures, overstimulation and maternal deprivation. Evidence, largely from animal studies, suggests stressful early experience negatively affects brain development. We also know that premature i ....Up to 50% of preterm infants will have one or more developmental difficulties. While medical complications are implicated in these problems, recent evidence points to the added effect of the infant's early environment. Hospitalised premature infants experience stress from necessary but painful hospital procedures, overstimulation and maternal deprivation. Evidence, largely from animal studies, suggests stressful early experience negatively affects brain development. We also know that premature infants find it difficult to handle stress as they are highly disorganised neurobehaviourally. The primary aim of this study is to assess the effectiveness of a parent-based intervention in enhancing neurobehavioural development at two years of age in very premature infants. It is predicted that this stress-reduction intervention will also enhance medical stability,normal brain development, parent-child interaction and parental mental health. The intervention to be trialled involves intensive training of parents of very premature infants, and in the 12 weeks following birth the parents will be the change agents. A randomised controlled trial comparing intervention and control groups will be undertaken to assess the effectiveness of this intervention. Assessments of early brain and 2 year intellectual, emotional and behavioural development will provide important outcome measures. A major strength of this study is the inclusion of advanced Magnetic Resonance Imaging (MRI) technology as it enables differences in brain development between the intervention and control group to be assessed, the association between brain and neurobehavioural development to be explored, and the impact of stress on early brain development to be investigated. This intervention is relatively simple and inexpensive, and would be a valuable contribution to neonatal care if found to be effective in enhancing brain and neurobehavioural development.Read moreRead less
Homeodomain Nkx2-5-dependent Negative Feedback Loop Important In Heart Development And Congenital Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,330,245.00
Summary
Congenital heart disease (CHD) is the cause of most deaths in children in the first year of life. We have identified a genetic pathway important for both normal cardiac development and CHD that involves the cardiac transcription factor Nkx2-5. This pathway controls a transition in embryos between cardiac cell specification and expansion. We will now explore the biochemical and genetic mechanisms underlying this pathway to help us understand CHD and identify its causative genes.