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
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
20 Year Study Of Skin Cancer In A Queensland Community
Funder
National Health and Medical Research Council
Funding Amount
$396,415.00
Summary
Skin cancers are by far the commonest cancers diagnosed in Australia. Even though it is known that sun exposure in excess causes skin cancers there are complexities about the causes, especially of basal cell carcinoma (BCC) -the major type of skin cancer- that are still not understood. Relative intensity of sun exposure and perhaps its timing with respect to age in life may well be critical factors. We aim to study these causes in very great detail by collating information that has been gathered ....Skin cancers are by far the commonest cancers diagnosed in Australia. Even though it is known that sun exposure in excess causes skin cancers there are complexities about the causes, especially of basal cell carcinoma (BCC) -the major type of skin cancer- that are still not understood. Relative intensity of sun exposure and perhaps its timing with respect to age in life may well be critical factors. We aim to study these causes in very great detail by collating information that has been gathered over a 20 year period in a community-based skin cancer study in Nambour, Qld as well as performing some laboratory tests on skin cancer tissue collected from participants. This 3-year project will enable the full realisation of the potential of this esource-20 years in the making- with its wealth of information for answering questions about skin cancer decelopment and preventability. It should finally provide us with a clearer rationale for 'prevention of skin cancer' than is currently available. In addition we shall assess the costs of treatment of skin cancer in general and for the individual, and how much preventive practices for skin cancer might save the health budget, by using the releavnt data collected from this community sample.Read moreRead less
The Effectiveness Of An Indicated Prevention Program For Anxiety
Funder
National Health and Medical Research Council
Funding Amount
$867,982.00
Summary
Generalised anxiety disorder (GAD) is a common disorder. In this research project, we evaluate the effectiveness of a new automated Internet program which is designed to reduce the risk of GAD and to promote self help. If found to be effective, this website will provide assistance to those at risk living in rural and remote areas without access to other resources, and individuals who prefer to seek help anonymously.
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
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
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
E-Cadherin Endocytosis In Morphogenesis: Recycling And Growth Factor Induced Uptake.
Funder
National Health and Medical Research Council
Funding Amount
$498,088.00
Summary
E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell ....E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell surface E-cadherin serves to regulate its role in adhesion. More recently, we and others have shown that E-cadherin is endocytosed in response to growth factors, in conjunction with the activated growth factor receptors themselves. E-cadherin can influence the trafficking and signaling of these receptor tyrosine kinases. This joint endocytosis is an elegant mechanism for the simultaneous downregulation of cell adhesion and activation of signaling for cell growth and motility. The growth and differentiation of epithelial cells during tissue patterning or morphogenesis relies critically on these endocytic pathways. Our research is aimed at defining the endosomes and cellular machinery involved in E-cadherin-receptor endocytosis, moreover we will pursue initial findings suggesting that there are different pathways and fates for E-cadherin endocytosed at the behest of different growth factors. We will study endocytosis during the processes of epithelial cyst formation and tubulation of cysts as an in vitro model for mammalian morphogenesis. These studies will provide important and novel information for understanding the roles of E-cadherin in adhesion and in growth factor signaling during epithelial morphogenesis. Ultimately these findings will be of relevance to epithelial development and the prevention of cancer.Read moreRead less
A Behavioural Intervention For The Adoption & Maintenance Of Physical Activity In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$334,955.00
Summary
For people with type 2 diabetes (T2DM) it is essential that blood glucose levels are managed well to reduce the risk of developing complications. Physical activity is essential for maintaining glucose levels because it helps make the muscles use glucose more effectively. In particular, being active through strength training not only improves blood glucose levels, but can be very effective for maintaining good physical functioning, which is known to be reduced by having T2DM. This study builds on ....For people with type 2 diabetes (T2DM) it is essential that blood glucose levels are managed well to reduce the risk of developing complications. Physical activity is essential for maintaining glucose levels because it helps make the muscles use glucose more effectively. In particular, being active through strength training not only improves blood glucose levels, but can be very effective for maintaining good physical functioning, which is known to be reduced by having T2DM. This study builds on our earlier research which demonstrated significantly improved blood glucose levels from a strength training program for older adults with T2DM. The strength training program is to be administered nationally in a research to practice trial (Lift for Life); however, the original research found that those who did not complete the program as it was intended (ie, poor adherence) did not show significant improvements in blood glucose levels. Furthermore, maintenance of strength training exercises after completion of the program was poor and resulted in return of blood glucose levels back to pre-starting levels. In people without diabetes, we have collected pilot data that shows that the use of behavioural strategies based on behavioural theories whereby each person's motivations and barriers are taken into consideration is more effective than the traditional one-treatment-fits-all approach. This study will evaluate the effectiveness of using behavioural strategies for improving adherence and maintenance to the Lift for Life strength training program (Enhanced L4L) for older adults with T2DM compared with the Standard L4L program. It will also follow-up participants 6 months later to determine the extent to which the changes in behaviour can be maintained. The study will provide information that will assist in the design, delivery and uptake of programs to improve treatment strategies in older adults with T2DM through the maintenance of healthier behaviours and lifestyles.Read moreRead less
Implementation And Evaluation Of A Diabetes Intervention Program In Indigenous Australian Communities.
Funder
National Health and Medical Research Council
Funding Amount
$173,625.00
Summary
Approximately 700,000 Australians have type 2 diabetes (also termed maturity-onset diabetes or non-insulin dependent diabetes), which is a condition associated with reduced lifespan, eye disease, heart disease, renal disease, stroke, and foot complications leading to amputation. Indigenous Australians are at particularly high risk, with over 30% of adults affected by this condition in a number of communities, associated with significant morbidity and mortality. Early diagnosis, healthy lifestyle ....Approximately 700,000 Australians have type 2 diabetes (also termed maturity-onset diabetes or non-insulin dependent diabetes), which is a condition associated with reduced lifespan, eye disease, heart disease, renal disease, stroke, and foot complications leading to amputation. Indigenous Australians are at particularly high risk, with over 30% of adults affected by this condition in a number of communities, associated with significant morbidity and mortality. Early diagnosis, healthy lifestyle modification and tight control of the blood sugar levels, blood pressure and cholesterol are the keys to preventing the complications of diabetes. Self-management is central to success, and education, support and encouragement play an important role. This research project incorporates an education program that has been developed in partnership with the indigenous health team at Cherbourg. Particular strengths include the emphasis on family involvement and community support. The central role of the indigenous health team will ensure continuity of benefit to the community. If proven to be effective, the program could be used as a model for interventions in other community settings to reduce the burden from type 2 diabetes in the indigenous Australian population.Read moreRead less