Teeth And Faces Of Australian Twins: A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$647,226.00
Summary
We are seeking support from the NHMRC to complete a longitudinal study of 250 pairs of twins, both identical and non-identical, whom we have examined at around 4-6 years of age when all the baby teeth were present in the mouth, then again at around 8-10 years of age when both primary and permanent teeth were present. We now plan to examine these twins again at around the age of 11-13 years when all the permanent teeth, except the wisdom teeth, are normally present. Records to be obtained from th ....We are seeking support from the NHMRC to complete a longitudinal study of 250 pairs of twins, both identical and non-identical, whom we have examined at around 4-6 years of age when all the baby teeth were present in the mouth, then again at around 8-10 years of age when both primary and permanent teeth were present. We now plan to examine these twins again at around the age of 11-13 years when all the permanent teeth, except the wisdom teeth, are normally present. Records to be obtained from the twins over the next three years will include dental examinations, dental impressions from which casts can be made, shed primary teeth, and intra- and extra-oral photographs. We will apply modern methods of genetic analysis to determine the importance of genetic and environmental influences on observed variation in several dental and facial features. We will also study the fascinating phenomenon of mirror imaging in twins, where one twin mirrors the other for one or more features. Longitudinal studies of twins, in which a large sample of children is studied over several years, provide a powerful means of determining how genes influence growth and development. As far as we are aware, ours is the only large-scale longitudinal study of dental and facial growth in twins being undertaken in the world at present. Once we have collected all the data and carried out analyses, we will gain a much better understanding of the factors that can influence development of the teeth and face, and be in a much better position to be able to predict those children who are most likely to develop malocclusions in later life.Read moreRead less
Hepatitis C Vaccine Preparedness Study: Investing In Infectious Disease Prevention
Funder
National Health and Medical Research Council
Funding Amount
$820,767.00
Summary
Injecting drug users (IDU) are a key target group for new vaccines designed to prevent hepatitis C virus (HCV) infection. This study will establish the feasibility of conducting HCV vaccine trials in IDUs by answering key scientific questions, generating data to inform trial design and evaluation, establishing a partnership between leading international researchers and the peak Australian body for people who inject drugs, and providing the foundation for a global HCV prevention trial network.
Efficacy And Safety Of Methylxanthines In Very Low Birth Weight Infants
Funder
National Health and Medical Research Council
Funding Amount
$221,136.00
Summary
With improving technologies and medications the numbers of very premature babies surviving to leave hospital has increased over the last two decades. However these babies are at increased risk of having brain damage in the form of mental retardation and cerebral palsy. These problems impose a major burden on the individuals, their families and society at large. This study attempts to identify whether or not a commonly used drug is safe in these babies or whether it contributes to brain damage in ....With improving technologies and medications the numbers of very premature babies surviving to leave hospital has increased over the last two decades. However these babies are at increased risk of having brain damage in the form of mental retardation and cerebral palsy. These problems impose a major burden on the individuals, their families and society at large. This study attempts to identify whether or not a commonly used drug is safe in these babies or whether it contributes to brain damage in some cases. Many premature babies have difficulty breathing by themselves because their brain does not send regular messages to their lungs telling them to expand. A class of drugs which includes caffeine has been shown to stimulate breathing in babies and has been thought to reduce the amount of support these babies require from a ventilator in the first weeks of life. The safety of these drugs has not been adequately demonstrated in premature babies and there is some evidence from animal studies that they may disrupt the developing brain. Results in human babies are inconclusive and concerns remain regarding the long term effects of caffeine. The question of whether caffeine usage increases the risk of mental retardation or cerebral palsy is a very important one given the almost universal usage of this or similar drugs in premature babies. We will find out whether babies given caffeine as newborns perform as well at 18 months of age as babies not given the drug.Read moreRead less
Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian c ....Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. An understanding of the way gene expression and hence tissue differentiation is altered after sex reversal will inform us about the causes and consequences of normal and abnormal sexual development, gonadal malignancies and infertility. The gonad is unusual in that two completely different organs can arise from an essentially identical primordium, so that errors in development lead to intersexual phenotypes. We will use our new experimental animal model to clarify these processes.Read moreRead less
Dissecting The Role Of Hedgehog Signalling In Chondrogenesis And Skeletal Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,739.00
Summary
There are close to 400 inherited disorders that affect how the skeleton develops, as well as a range of injury and age-related skeletal defects. There is much interest in treating such abnormalities with artificial bone grown outside the body. In order to achieve this aim we must understand all of the processes involved in producing and maintaining bone within the body. We are using both mouse and cell culture models of skeletal development to increase our understanding of these processes.
THE ROLE OF UBIQUITIN LIGASE ADAPTOR PROTEIN NDFIP1 IN NEURONAL DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$581,813.00
Summary
Many brain diseases are characterized by faulty connections between nerve cells (neurons), in some cases caused by the inability to remove unwanted proteins from the neuron. This function is carried out by the ubiquitin-proteasome system (UPS). We have evidence that a UPS protein called Ndfip1 is important for forming functional brain circuits. We aim to discover whether neuron growth, branching and connectivity is promoted by Ndfip1 targeting of PTEN (phosphatase with tensin homology) to the UP ....Many brain diseases are characterized by faulty connections between nerve cells (neurons), in some cases caused by the inability to remove unwanted proteins from the neuron. This function is carried out by the ubiquitin-proteasome system (UPS). We have evidence that a UPS protein called Ndfip1 is important for forming functional brain circuits. We aim to discover whether neuron growth, branching and connectivity is promoted by Ndfip1 targeting of PTEN (phosphatase with tensin homology) to the UPS.Read moreRead less
Gudaga Project: Understanding The Health, Development, And Service Use Of Aboriginal Children In An Urban Environment
Funder
National Health and Medical Research Council
Funding Amount
$1,424,845.00
Summary
The Gudaga project is a birth cohort of Aboriginal children that will be followed from 18 months to 5 years and describe their health, development and service (health and children's) use. This is the first study of its kind in Eastern Australia. The research team are working closely with stakeholders in Aboriginal health care including the Aboriginal community to implement the research. The research will contribute to services for Aboriginal children in the local and wider community.
Body Segment Identity Specification By The Transcription Regulator, Moz
Funder
National Health and Medical Research Council
Funding Amount
$366,301.00
Summary
One in 28 newborns have birth defects. Cleft palate and aortic arch defects are among the most common, always requiring surgery and often causing lethality. We propose to study a protein, Moz, which is essential for palate and aortic arch development. Moz (Monocytic leukaemia zinc finger protein) was first identified in human chromosomal abnormalities causing particularly aggressive forms of childhood and adult leukaemia. We have shown previously that Moz is essential for the formation of blood ....One in 28 newborns have birth defects. Cleft palate and aortic arch defects are among the most common, always requiring surgery and often causing lethality. We propose to study a protein, Moz, which is essential for palate and aortic arch development. Moz (Monocytic leukaemia zinc finger protein) was first identified in human chromosomal abnormalities causing particularly aggressive forms of childhood and adult leukaemia. We have shown previously that Moz is essential for the formation of blood stem cells. Moz can regulate the activity of genes, but which genes it regulates in vivo is unknown. In the absence of Moz, mice are born with a cleft palate, lack the thymus, where immune cells are instructed, and fail to form the lung blood circulation, so that they are unable to supply their blood with oxygen after birth. Moz deficiency also causes defects of the vertebrate column, such that individual vertebrae acquire the appearance of their neighbours. These symptoms are typical for a general defect in positional information of individual body segments with respect to their location along the body axis. We will investigate the molecular mechanisms that require Moz in patterning of the body axis. This project will characterize a genetic mechanism that is crucial for normal development of the palate, the aorta and the vertebrate column.Read moreRead less
Molecular Genetics Of Sex Determination And Gonad Development
Funder
National Health and Medical Research Council
Funding Amount
$539,000.00
Summary
Disorders of sexual development are among the most common forms of birth defects in humans (1 in 4,000 births). Many other childhood conditions with this incidence warrant prenatal diagnosis or neonatal screening. These disorders often result in infertility, genital abnormalities and gender mis-assignment. Uncertainty about a child s gender at birth can be very traumatic physically and psychologically for the individual and family concerned. There are profound consequences in later life for the ....Disorders of sexual development are among the most common forms of birth defects in humans (1 in 4,000 births). Many other childhood conditions with this incidence warrant prenatal diagnosis or neonatal screening. These disorders often result in infertility, genital abnormalities and gender mis-assignment. Uncertainty about a child s gender at birth can be very traumatic physically and psychologically for the individual and family concerned. There are profound consequences in later life for the affected individual. 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 project 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.Read moreRead less
The Role Of Scube Genes In Hedgehog Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
Cancer often results form the miss-regulation and-or mutation of genes that control tissue formation in the developing embryo. Particular sets of genes combine to form a signal transduction pathway that coordinates the cell's response to its environment during the course of normal fetal growth. One such pathway is called the Hedgehog signal transduction pathway which has been shown to coordinated cell division and patterning within malignant and normal tissues. Genes encoding components of this ....Cancer often results form the miss-regulation and-or mutation of genes that control tissue formation in the developing embryo. Particular sets of genes combine to form a signal transduction pathway that coordinates the cell's response to its environment during the course of normal fetal growth. One such pathway is called the Hedgehog signal transduction pathway which has been shown to coordinated cell division and patterning within malignant and normal tissues. Genes encoding components of this pathway are mutated in the most common forms of human cancers. Understanding how this pathway is regulated is critical to designing strategies to treat the onset and progression of these cancers. The studies outlined in this grant plan to study a new component of this pathway that we have identified in our laboratory, in an easy to study vertebrate model, the zebrafish embryo. We plan to study how this class of proteins, termed scube proteins, acts to control activation of the pathway. We hope this will lead to a fuller understanding of this process, and at the same time help understand the nature of the end result of the patterning process within the muscle cells that we are studyingRead moreRead less