Mechanisms Guiding Pathfinding And Positioning Of Cortical Interneurons
Funder
National Health and Medical Research Council
Funding Amount
$621,606.00
Summary
Brain disorders place an economic and social burden on Australia and the personal costs of these illnesses are immeasurable. Several brain abnormalities are caused from the failure of neurons to position themselves in the correct location when the brain develops. Our study aims to discover how neurons move and what factors influence this process. It provides an understanding of normal brain development, as well as providing insight into what may go wrong in the formation of brain diseases.
Understanding How Language And Reading Problems Develop: A Population-based Longitudinal Study From Infancy To Age 7
Funder
National Health and Medical Research Council
Funding Amount
$667,507.00
Summary
Early language and reading problems are common and therefore significant public health problems. They are disabling and have life-long implications for oral and written communication skills, social and emotional well-being, cognition, behaviour, academic achievement and employment. This study will address the following three problems: 1. To date no study has documented how language and reading problems develop from infancy (8 months) through to school age (7 years). 2. Little is known about risk ....Early language and reading problems are common and therefore significant public health problems. They are disabling and have life-long implications for oral and written communication skills, social and emotional well-being, cognition, behaviour, academic achievement and employment. This study will address the following three problems: 1. To date no study has documented how language and reading problems develop from infancy (8 months) through to school age (7 years). 2. Little is known about risk factors, identified early in infancy and childhood, that can be reliably used to predict language and reading problems later in childhood. 3. The relationships between language difficulties and reading problems are poorly understood. Therefore, we currently have no satisfactory methods for reliably detecting which children at much younger ages are at risk of later language disorders or reading problems. Without this information it is impossible to develop effective prevention and early intervention programs. These programs are critical if we are to: a) Prevent language and reading problems from occurring, thereby reducing the prevalence of the problem b) Intervene early in childhood, thereby reducing in the longer term the burden and cost associated with language and reading problems. The proposed study builds on an existing substantial investment by the NHMRC in the Early Language in Victoria Study (ELVS). It will provide a world-first description of the evolution of language difficulties and reading problems from infancy through to school age within a single population cohort.Read moreRead less
The Role Of Rnd Genes During Cortical Neurogenesis And Cell Migration
Funder
National Health and Medical Research Council
Funding Amount
$410,384.00
Summary
In order for the brain to function properly, tens of billions of neurons within it first have to be born, then find their proper location before connecting with other neurons in a highly ordered fashion. Failure of these key processes heavily impacts on subsequent brain function, and have been shown to underlie several disorders including epilepsy. This study will investigate how members of the Rnd gene family control cell production and positioning within the developing brain.
The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Defining Genetic And Epigenetic Variation During Early Development
Funder
National Health and Medical Research Council
Funding Amount
$996,075.00
Summary
We all began life with a set of genes inherited from our parents. However, it's now known that from the time we were in the womb onwards that genes can be turned off and on by the environment or even completely lost or gained. Even what your mother ate or how she behaved while she was pregnant could have influenced your future health. Because people are so different, we are studying the subtle differences between twins to tease out the factors that may influence our genes and our health.
Identification Of Novel Mechanisms Governing Stage-specific Regulation Of The Human Globin Genes
Funder
National Health and Medical Research Council
Funding Amount
$481,826.00
Summary
Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases worldwide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing embryo, fetal hemoglobin. We have identified key factors important for fetal gene expression. Our goal is to translate these findings into therapies for the hemoglobin disorders.
Migration And Differentiation Of Enteric Neuron Precursors
Funder
National Health and Medical Research Council
Funding Amount
$385,116.00
Summary
There are many millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called neural crest cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the ....There are many millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called neural crest cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the entire small and large intestines by neural crest cells takes over 4 days, and in humans the process probably takes at least one week. It is essential that the neural crest cells colonise the entire gastrointestinal tract, since regions of intestine lacking neural crest cells (and hence nerve cells) cannot function and intestinal contents build up in front of the region lacking nerve cells. This condition is found in some babies (Hirschsprung's disease), and it can only be treated by surgically removing the region lacking nerve cells. It is therefore essential that migratory neural crest cells colonise the entire gastrointestinal tract. Currently, little is known about the mechanisms controlling the migration of neural crest cells, and whether a) particular molecules within the gut wall are important for migration, and-or b) the migratory behaviour of the neural crest cells is regulated mostly by the neural crest cells themselves. In this study we will take time-lapse images of neural crest cells migrating through the gut of embryonic mice to identify the factors that are important for the migration. After the neural crest cells have colonised the entire intestine, they develop into different types of nerve cells. We will also examine some of the factors affecting the development of different types of nerve cells.Read moreRead less
Predictors And Correlates Of Developmental Language Problems: A Longitudinal Study From Infancy To Pre-school Age
Funder
National Health and Medical Research Council
Funding Amount
$537,750.00
Summary
Language impairment is a disabling condition, thought to affect between 7% and 15% of 4 year old children. It has serious and lasting implications for social and emotional development, cognition, behaviour and literacy. A link has been demonstrated between language impairment and later psychiatric disorders in adolescence and adulthood. Given the potential of enhancing the language development of young children, it is critical that effective prevention and early intervention programs are availab ....Language impairment is a disabling condition, thought to affect between 7% and 15% of 4 year old children. It has serious and lasting implications for social and emotional development, cognition, behaviour and literacy. A link has been demonstrated between language impairment and later psychiatric disorders in adolescence and adulthood. Given the potential of enhancing the language development of young children, it is critical that effective prevention and early intervention programs are available. However, current knowledge is liminted in that there are no entirely satisfactory methods for detecting children who at much younger ages, 8 months, 12 months, 2 years and 3 years, are at risk of later impairment. In this study we aim to: examine the risk factors (many are thought to exist) that contribute to language impairment learn more about the natural history of this disabling disorder in children between 8 months and 4 years of age Ultimately, we aim to identify early signs that might warn health professionals and parents of language impairment so that such problems can be detected much earlier. Early identification will mean that help is available at an earlier age to children who currently go on to have persisting and extremely disabling language impairment.Read moreRead less
Why Does Early Life Stress Aggravate Limbic Epileptogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$540,116.00
Summary
High rates of anxiety and depression occur in individuals with temporal lobe epilepsy (TLE), the most common form of focal epilepsy in adults. Rats that have experienced early life stress show increased anxiety, decreased seizure thresholds and accelerated epilepsy as adults. We have important leads to mechanisms. The proposed study will better understand the mechanisms connecting early life stress and psychiatric disease to adult TLE, and to test interventions that may counteract these effects.
A Population-based Cohort Investigation Of Postnatal Microbial Experience, Immune Programming And Allergic Disease Risk
Funder
National Health and Medical Research Council
Funding Amount
$1,511,471.00
Summary
This is a population-based longitudinal investigation of the early life host-environment interactions that influence development of the immune system, and the risk of allergic disease. Importantly, this is one of the first studies designed to examine epigenetic programming of the infant immune system in the population setting. Thus we will be able to conduct robust tests of several critical hypotheses that will inform the prevention of allergic disease.