Molecular Control Of Cell Proliferation In Early Mouse Development
Funder
National Health and Medical Research Council
Funding Amount
$338,009.00
Summary
Elucidation of cell cycle regulation in the proliferating pluripotent cells of the early mammalian embryo is likely to have important impact on basic scientific knowledge, and on the development of novel therapeutic strategies. Investigation of this problem, in vitro and in vivo, requires specialist skills in cell cycle analysis, and experimental manipulation of mammalian embryos and pluripotent cells. This application will seek to address these fundamental issues of early development and cell p ....Elucidation of cell cycle regulation in the proliferating pluripotent cells of the early mammalian embryo is likely to have important impact on basic scientific knowledge, and on the development of novel therapeutic strategies. Investigation of this problem, in vitro and in vivo, requires specialist skills in cell cycle analysis, and experimental manipulation of mammalian embryos and pluripotent cells. This application will seek to address these fundamental issues of early development and cell proliferation using molecular approaches. The general aims will be: 1. to obtain a detailed description of cell cycles in pluripotent and differentiating cells of the mouse embryo 2. use this information to build a molecular description of cell cycle events during early embryogenesis 3. investigate the relationship between rapid cell proliferation in the embryo and pluripotencyRead 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
Early Detection Of Infants And Young Children With Autism
Funder
National Health and Medical Research Council
Funding Amount
$268,250.00
Summary
Autism is a severely handicapping condition adversely affecting social interaction, communication, behaviour, interests, and activities. Autism requires treatment at an early age (before 4 years). Despite finding that parents notice problems with their child's development within the first 2 years, on average diagnoses are made around 6 years of age. Treatment for autism should begin as early as possible to improve outcome. Diagnosis requires specialist assessment and these services are limited. ....Autism is a severely handicapping condition adversely affecting social interaction, communication, behaviour, interests, and activities. Autism requires treatment at an early age (before 4 years). Despite finding that parents notice problems with their child's development within the first 2 years, on average diagnoses are made around 6 years of age. Treatment for autism should begin as early as possible to improve outcome. Diagnosis requires specialist assessment and these services are limited. Therefore it is not possible to undertake such assessments with all children who have developmental problems. This project therefore proposes to evaluate a method for screening large populations of children for autism, thus enabling timely and more appropriate referral to assessment services. Previous work by the investigators has developed a potential screening tool (DBC Early Screen) for autism in young children under 4 years with developmental delay that has high levels of accuracy in identifying those infants and children who are at risk of autism and require specialist assessment. This project proposes to undertake a community field trial to assess the accuracy and reliability of this early screen and to establish its suitability for wide use as a population screening tool. The preliminary testing of DBC Early Screen demonstrated that a community field trial was feasible. The results of this study will facilitate the referral of infants and young children to specialist autism assessment services, thus enabling the commencement of appropriate early intervention for children and their families from an early age.Read moreRead less
Long-term Efficacy Of An Oral Health Promotion Program In The Prevention Of Early Childhood Caries.
Funder
National Health and Medical Research Council
Funding Amount
$165,664.00
Summary
The aim of the project is to test the long-term efficacy of oral health promotion program, the purpose of which is to lower the prevalence of tooth decay among young children. Tooth decay affects approximately 1 in 6 children by age of 3 years and 1 in 2 children by age of 5 years. The disease negatively influences all aspects of quality of life of child. Tooth decay is associated with infection, pain, and frequent hospitalisation. The proposed project is a follow-up of an randomised controlled ....The aim of the project is to test the long-term efficacy of oral health promotion program, the purpose of which is to lower the prevalence of tooth decay among young children. Tooth decay affects approximately 1 in 6 children by age of 3 years and 1 in 2 children by age of 5 years. The disease negatively influences all aspects of quality of life of child. Tooth decay is associated with infection, pain, and frequent hospitalisation. The proposed project is a follow-up of an randomised controlled trial (RCT), which started with enrolment of pregnant women. They were randomised into the test and control groups. Mothers in test group received 3 round of preventive oral health information in the form of anticipatory guidance, the first round at enrolment, the second and third at 6, 12 months of age of child respectively. The information was mailed to their home address. All children were examined at age of 20 months of age. The children in the test group had lower prevalence of tooth decay compared to children in control group, (test group 1,7%, control group 9.6%). While the oral health information was effective in preventing decay at 20 months, longer-term follow-up is highly desirable. Therefore, we plan to follow-up the oral health of the children at 5 - 6 years old. It is anticipated, that 75% mothers from the trial will be contactable and will continue with their participation in the study. A third comparative group of children at the same age will be drawn from database of the South Australian School Dental Services to check if the children in the trial are representative of all SA school children. All children will be examined by dentists or school dental therapists after they enter school. The prevalence of the tooth decay and its mangement will be examined and compared among children from test and control groups and children from community.Read moreRead less
The Ontogeny Of TLR Mediated Innate Immune Function In Normal And Atopic Children
Funder
National Health and Medical Research Council
Funding Amount
$463,328.00
Summary
Bacteria are first recognised by the immune system though primitive innate immune pathways which are highly conserved through evolution. The activation of these pathways is critical for the maturation of the immune system. This may explain the rise in immune diseases with cleaner environments (and less innate immune activation). We speculate that functional differences (as a result of environmental or genetic factors) are implicated in the rising rates of allergic disease. This is the first stud ....Bacteria are first recognised by the immune system though primitive innate immune pathways which are highly conserved through evolution. The activation of these pathways is critical for the maturation of the immune system. This may explain the rise in immune diseases with cleaner environments (and less innate immune activation). We speculate that functional differences (as a result of environmental or genetic factors) are implicated in the rising rates of allergic disease. This is the first study to document normal maturation of these innate pathways in early childhood, and to compare this in allergic and nonallergic children. We will do this using existing samples collected as part of previous cohort studies. This study is the logical next step in the quest to define allergy pathogenesis. Whatever the outcome, the findings will be of enormous significance. A better understanding of the development of these pathways is also likely to contribute to more avenues for better-targeted treatment and prevention.Read moreRead less
Immunomodulatory Effects Of Omega-3 Polyunsaturated Fatty Acids : Role In Allergy Prevention In Infancy
Funder
National Health and Medical Research Council
Funding Amount
$537,600.00
Summary
The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed f ....The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed for the first time that n-3 PUFA may have more significant effects in very early life before immune responses are fully established. We confirmed that maternal fish oil supplementation (n-40) resulted in significantly higher n-3 PUFA levels in newborns (compared to those with no supplements, n-43), and this was related to reduced immune responses to allergens (such as house dust mite, cat and egg). These observations suggest that n-3 PUFA can modify early immune development. Although this previous study was designed to assess immune outcomes (rather than clinical outcomes) we collected preliminary clinical data for the purposes of this application. We observed a consistent trend for less allergic symptoms and sensitisation in the supplementation group. These observations clearly warrant this proposed study to confirm these clinical effects, and to assess the mechanisms of action in considerably more detail. In this proposed study we will compare the effects of fish oil (n-165) or placebo (n-165) in early infancy (from 0-6 months of age). This much larger population will allow us to determine if increasing dietary n-3 PUFA is a way of reducing the chance of allergy in families where there is a high genetic risk. Approximately 40% of infants in Australia will go on to develop asthma or allergies. Strategies such as this that reduce the risk (even slightly) or the severity of disease expression could have enormous impact in this global context at relatively little cost.Read moreRead less
Relating Genetic, Biological, And Behavioural Markers Of Early Conduct Problems In Young Females
Funder
National Health and Medical Research Council
Funding Amount
$403,639.00
Summary
Child CPs are the first identifable sign of ongoing mental health problems. Most research is done with males, but they are also the most common early markers in females. We are in the unique position to conduct the first test of the relationships between specific genetic risk, neurobiological markers and psychological functioning in females. Findings will inform models of genertic vulnerability, the relationship of genetic risk to basic information processing styles in at-risk children.
Relating Genetic, Biological, And Behavioural Markers Of Early Vulnerability In Conduct Problem Children.
Funder
National Health and Medical Research Council
Funding Amount
$439,183.00
Summary
This research will conduct the first test of specific genetic risk in a large and representative sample of young conduct problem children. These children represent the first readily identifiable group that are at high risk for ongoing mental health problems in our community. It is highly likely that within their numbers are heterogeneous subgroups that will take very different trajectories through life. The current study builds on several years of developmental research in which we have develope ....This research will conduct the first test of specific genetic risk in a large and representative sample of young conduct problem children. These children represent the first readily identifiable group that are at high risk for ongoing mental health problems in our community. It is highly likely that within their numbers are heterogeneous subgroups that will take very different trajectories through life. The current study builds on several years of developmental research in which we have developed methods for identifying different phenotypes within the group. The study will identify genetic markers of these subtypes and relate these to emotional processing as a general model of risk in the development of mental health problems and antisocial behaviour. Findings will inform models of genetic vulnerability, and more importantly, the relationship of genetic risk to basic information processing styles in at-risk children, thus aiding methods for early detection, early intervention and prevention.Read moreRead less