Hedgehog Signalling In Limb And Craniofacial Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,544.00
Summary
Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in b ....Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in both limb and face development. Based on the organs in which our genes of interest are active, we believe that they will also play key roles in embryonic development of the limbs, face and other organs. We now plan to investigate the regulation of a subset of these genes based on analysis in mouse models of limb and face development. In addition, we have chosen to further analyse the function of a completely novel gene we have identified which our preliminary studies suggest may play a role in the normal development of the lip and palate. These studies have the potential to shed light on the processes governing how organs develop, as well as on the molecular basis of common birth defects such as polydactyly (extra fingers and toes) and cleft palate.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
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.
Cognitive Impairments And Post Traumatic Stress Symptoms In Children With Traumatic Brain Injury: A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$482,250.00
Summary
Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic ....Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic stress, it is not clear how these interact, how they influence long-term outcomes, and what factors such as pre-injury functioning and family support and distress mediate outcomes. These issues are very important since effective rehabilitation of children following traumatic brain injury is essential to maximise long-term functioning and minimise disability. To be effective, rehabilitation must be guided by the knowledge about key factors that determine the recovery process. This study aims to provide answers to these questions by following two cohorts of children (aged 6-14) over 18 months after receiving a traumatic brain injury. In total 240 children will be recruited from Brisbane and Melbourne hospitals. They will be assessed at three, six, twelve and eighteen months post-injury using measures of cognitive, psychological and social functioning. Information on parent distress and behaviours will also be obtained. The information obtained will provide the basis for the development of a specific rehabilitation strategy for children with traumatic brain injury, including information on strategies to help prevent any confounding impact of post-traumatic stress on recovery.Read moreRead less
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
Impact Of DTP Schedules On The Immunogenicity Of 2 Doses Of 13v-PCV Followed By An Early Booster
Funder
National Health and Medical Research Council
Funding Amount
$2,651,687.00
Summary
This project aims to come up with a vaccination schedule to make pneumococcal vaccines more effective and affordable for Fiji and other developing countries. We will evaluate schedules involving a 2 dose primary series in early infancy with a booster at 9 months of age. We will compare the immune responses to 3 different primary series and 2 booster options. The results of this project will be used to provide advice, at global and country levels, regarding introduction of pneumococcal vaccines.
Understanding Changes In The Mammalian Prenylome Induced By Statins And Prenyltransferase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Prenylation, the covalent attachment of isoprenoid lipids to proteins, is widespread in mammalian cells. Essential for a protein's normal function, it contributes to the progression of cancer and inflammation. We have developed a novel technology to identify all prenylated proteins in the cell. Aided by this method, we will analyse the effect of statins and anti-cancer drugs on protein prenylation. This will provide guidance in identifying a more effective clinical use for them.
PrtFII, A Streptococcus Pyogenes Fibronectin Binding Protein, And Invasive Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$296,540.00
Summary
Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin bind ....Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin binding protein, than those from uncomplicated skin sores. In this application we propose to extend this observation and compare biochemical properties of PrtFII from strains belonging to the above two sets of collections. We hypothesise that PrtFII from invasive strains bind to fibronectin more tightly than the proteins from strains that cause uncomplicated infection. We also will test whether sera from invasive disease cases have lower titre of antibodies to the conserved region of PrtFII than sera from uncomplicated cases. A streptococcal vaccine by necessity has to be a multi-component vaccine to cover a wide spectrum of diseases and epidemiological differences. The study proposed here may provide a basis to argue whether or not to include PrtFII in such a multi-component vaccine.Read moreRead less