Environmental, Socio-behavioural And Biological Predictors Of Early Childhood Caries: A Rural Birth Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$495,432.00
Summary
In Australia, up to 75% of children have dental decay at five years of age. It is substantially worse in rural parts of Australia, where fluoride is not added to the water supply. Also, the rate of caries increases as socioeconomic status decreases. This study aims to describe the natural history of dental caries from birth to 18 months. It will also examine the environment, behaviours and biology that these infants are exposed to. This data has never been collected before and will therefore pro ....In Australia, up to 75% of children have dental decay at five years of age. It is substantially worse in rural parts of Australia, where fluoride is not added to the water supply. Also, the rate of caries increases as socioeconomic status decreases. This study aims to describe the natural history of dental caries from birth to 18 months. It will also examine the environment, behaviours and biology that these infants are exposed to. This data has never been collected before and will therefore provide a unique contribution to our knowledge and understanding of the development of dental decay in young children. This data is crucial for the development of interventions to prevent dental decay and address health inequalities. The study will examine infants teeth as they come into their mouths and collect questionnaire and saliva data from parents and infants following birth at 1, 6, 12 and 18 months. It is a partnership between the maternal and child health nurses of the western rural areas of Victoria (Ballarat, Ararat, Stawell and Horsham) and a national team of child health, dental researchers and statisticians drawn from the School of Health and Social Development at Deakin University, the Murdoch Children's Research Institute and The Royal Children's Hospital's Department of Paediatric Dentistry, The University of Melbourne, The University of Western Australia, Griffith University and the Queensland Government. The proposed study will make a substantial contribution to the understanding of early childhood caries by providing unique data on its natural history, the relationship between caries and risk and protective factors and the relative contribution of these factors to dental decay. Additionaly, it will include the latest measurement developments for quantifying microflora species and clinical caries outcomes. The comprehensiveness of this approach has been called for internationally, but has not yet been attempted.Read moreRead less
Polymicrobial Interactions In A Biofilm Of Periodontopathic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$474,517.00
Summary
Chronic periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. Three bacterial species in a biofilm (dental plaque) have been closely associated with chronic periodontitis in human ....Chronic periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. Three bacterial species in a biofilm (dental plaque) have been closely associated with chronic periodontitis in humans and a fourth bacterial species has been suggested to assist colonisation of the biofilm by the three pathogenic species. The aim of this project is to use DNA microarray and proteomic techniques to study the interaction of the four bacterial species grown together in a polymicrobial biofilm. In particular genes of two of the pathogens, Porphyromonas gingivalis and Treponema denticola, important for biofilm formation and virulence in an animal model will be identified. This information will provide insight into the molecular processes of dental plaque formation and therfore molecular targets for the development of specific inhibitors that may have utility in the treatment and prevention of chronic periodontitis.Read moreRead less
Porphyromonas Gingivalis Cysteine Proteinases In Modulation Of Cell-mediated Immune Response In Periodontitis
Funder
National Health and Medical Research Council
Funding Amount
$228,000.00
Summary
Chronic inflammatory diseases of the tissues supporting the teeth comprise some of the most widespread and common diseases to affect mankind. Recent research has indicated the major contributor to the most common form of destructive periodontal disease is the bacterium Porphyromonas gingivalis. This organism produces powerful enzymes which overcome the body's attempts to neutralise them. It is also known that the destructive phase of the disease is characterised by a change in the behaviour of t ....Chronic inflammatory diseases of the tissues supporting the teeth comprise some of the most widespread and common diseases to affect mankind. Recent research has indicated the major contributor to the most common form of destructive periodontal disease is the bacterium Porphyromonas gingivalis. This organism produces powerful enzymes which overcome the body's attempts to neutralise them. It is also known that the destructive phase of the disease is characterised by a change in the behaviour of the immune system cells which accumulate in the diseased tissues. This is manifest as a loss of protective immunity and replacement by ineffective or even tissue damaging responses. Critical in directing the pattern of behaviour of the immune system cells are the potent messenger molecules or cytokines which pass between cells. We have demonstrated that the bacterial proteinases can destroy a critical messenger molecule that instructs the defensive phagocytic cells to attack bacteria. These cells in return normally send a powerful signal back to the controlling T lymphocyte to amplify the protective signals. Associated bacterial molecules stimulate more secretion of messenger molecules which are paradoxically destroyed by the bacterial enzymes. This could cause chaos in the local tissue environment. Further, the bacterial proteinases can also eliminate some important surface molecules of T lymphocyte that are important in the activation process. The effect of this could produce impairment of T lymphocyte at periodontal sites. The planned research will define how the proteinases modulate T lymphocyte immune response. Further, the relation between the capacity of the bacterial enzymes to disrupt the vascular cells and the progression of periodontitis will also be determined.Read moreRead less
Dental diseases affecting the gums (periodontal diseases) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised chewing function. If left untreated, the associated loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cell ....Dental diseases affecting the gums (periodontal diseases) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised chewing function. If left untreated, the associated loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cells and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.Read moreRead less
Tooth Emergence And Oral Streptococci Colonisation: A Longitudinal Study Of Australian Twins
Funder
National Health and Medical Research Council
Funding Amount
$521,600.00
Summary
We plan to include over 500 Australian families of twins in this 5-year study and to collect records of tooth emergence, cheek cells for DNA analysis, dental plaque samples for microbiological analysis, as well as other information from questionnaires. Firstly, we want to learn how genetic and non-genetic factors influence the timing and sequence of emergence of primary (baby) teeth. Most children get their baby teeth between the ages of 6 months and 2.5 years, but sometimes they appear earlier, ....We plan to include over 500 Australian families of twins in this 5-year study and to collect records of tooth emergence, cheek cells for DNA analysis, dental plaque samples for microbiological analysis, as well as other information from questionnaires. Firstly, we want to learn how genetic and non-genetic factors influence the timing and sequence of emergence of primary (baby) teeth. Most children get their baby teeth between the ages of 6 months and 2.5 years, but sometimes they appear earlier, even at birth, and some children don't get all their baby teeth until about 4 years. By studying identical twins and non-identical twins we will be able to work out whether genetic factors are most important in determining this variation or whether other factors such as diet or illness also play a significant role. Secondly, we want to find out whether there is a relationship between the timing of emergence of the primary teeth and the growth of bacteria in the mouth that may lead to dental decay. It seems that the most likely source of the bacteria that can cause dental decay is a baby's mother and that children infected before three years of age are more likely to get dental decay subsequently. We will determine when decay-producing bacteria first appear in the mouth and check whether the same types of bacteria are present in twins and their mothers. This information will enable us to sort out whether the process that allows bacteria to become established around the teeth has a strong genetic basis or not. If we can gain a better understanding of how genetic and environmental factors influence dental development, we will be in a better position to manage individuals with altered tooth emergence that can lead to crowded teeth. Furthermore, if we can demonstrate a link between tooth emergence, growth of oral bacteria, and development of dental decay, we should be able to determine the most effective time to introduce preventive measures to control dental disease.Read moreRead less
Molecular Characterization Of The Gingipains Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$394,000.00
Summary
Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic perio ....Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic periodontitis. We have identified a major virulence factor of P. gingivalis which is an extracellular complex of proteins involved in binding and destroying host proteins. The aim of this proposal is to characterize the secretion, molecular processing and assembly of the cell surface complex using state-of-the-art proteomic techniques. This study will provide valuable insight into the molecular processes of a bacterial pathogen that leads to virulence. Detailed knowledge on the unique molecular events involved in secretion, processing and assembly of a major virulence factor will provide molecular targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic and-or as part of a preventive regime or maintenance program for the control of chronic periodontitis. Further, the molecular insight that will result from this study will have broader application in the understanding of virulence factor processing of a Gram-negative pathogen that will provide paradigms for other bacterial pathogens.Read moreRead less
Characterization Of Casein Phosphopeptide Amorphous Calcium Fluoride Phosphate As A Remineralization System
Funder
National Health and Medical Research Council
Funding Amount
$493,514.00
Summary
Dental caries (tooth decay) remains a major public health problem in Australia with an economic burden in excess of $1 billion p.a. The overall aim of this project is the development of a novel remineralizing agent (casein phosphopeptide stabilized amorphous calcium fluoride phosphate) for the remineralization of early tooth decay lesions (white spot lesions). The project will involve the testing of the ability of the novel remineralization system to remineralize (repair) white spot lesions in v ....Dental caries (tooth decay) remains a major public health problem in Australia with an economic burden in excess of $1 billion p.a. The overall aim of this project is the development of a novel remineralizing agent (casein phosphopeptide stabilized amorphous calcium fluoride phosphate) for the remineralization of early tooth decay lesions (white spot lesions). The project will involve the testing of the ability of the novel remineralization system to remineralize (repair) white spot lesions in vitro and in situ. The project also involves the detailed characterization of the molecular interactions of the components of the remineralizing system using NMR spectroscopy and other techniques. It is anticipated that this project will result in the development of a system with substantialy superior properties for the non-invasive treatment (reversal) of white spot lesions and may ultimately lead to the development of a novel system for the treatment and prevention of tooth decay.Read moreRead less
Chronic periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden. The bacterium Porphyromonas gingivalis has been identified as a major pathogen in the development of chronic periodontitis. We have identified and characterised a major virulence factor of P. gingivalis; a complex of proteins whic ....Chronic periodontitis is a bacterial-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden. The bacterium Porphyromonas gingivalis has been identified as a major pathogen in the development of chronic periodontitis. We have identified and characterised a major virulence factor of P. gingivalis; a complex of proteins which is involved in binding and destruction of host tissue. We have shown that this protein complex when used as a vaccine protects against P. gingivalis induced disease in animal periodontitis models. We have identified the regions (peptides) of the protein complex that allow the bacteria to bind to host tissue and blood proteins and these and other complex-related peptides when used as vaccines reduced disease in animal models. Recently, a consortium involving T.denticola, T.forsythia and P.gingivalis has been closely associated with the development of periodontitis in humans. We have shown that a mixture of these bacteria have greater pathogenicity in an animal periodontitis model than any one bacterium individually at the same total dose. The aim of this project is to identify epitopes in T. denticola and T. forsythia and to combine them with those of P. gingivalis into a multipathogen vaccine using techniques we have patented. The efficacy of the multipathogen vaccine to produce an immume response which is effective against the three bacteria will be investigated. The significance of this work is that we will produce a fully synthetic vaccine that may have utility in the prevention of periodontitis and the platform technology developed may have utility for a range of diseases associated with multiple bacterial pathogens.Read moreRead less
Tissue Regeneration In Oral Health: Regenerating Damaged Oral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$575,833.00
Summary
The regeneration of damaged dental tissues is an emerging area in oral health-based research and is increasingly becoming the forefront of medical-dental interdisciplinary investigations. This idea of repairing damage follows Dr Fiona Wood's unique concept of growing large amounts of specific cells in the lab and spraying them onto damaged tissue, which effectively assists in the repair of the damaged organ. This approach can be similarly used in the dental field by applying prosthetic implants ....The regeneration of damaged dental tissues is an emerging area in oral health-based research and is increasingly becoming the forefront of medical-dental interdisciplinary investigations. This idea of repairing damage follows Dr Fiona Wood's unique concept of growing large amounts of specific cells in the lab and spraying them onto damaged tissue, which effectively assists in the repair of the damaged organ. This approach can be similarly used in the dental field by applying prosthetic implants with cells and growth factors, thus enhancing the regeneration of the damaged dental tissue. Artificial replacement of missing teeth has significant limitations when compared with the natural, original tissues in terms of function and appeal. Bridges and dentures have been used for centuries in dentistry but require periodic maintenance or even replacement after a period of time due to usage or loss of adaptation. Thus, if implants and bridgework can be eliminated, so too will be the problems and costs associated with them. This benefit is specifically aimed at the regional community and the public sector, as these patients are generally not in a financial position to restore missing teeth with bridgework, let alone implants. Our aims are: 1. Examine the function of two recently identified growth factors, Osteoclast-Derived Osteoblastic Factor and Emilin and Multimerin-2, through their effect on paradental in vitro cell regeneration. 2. To assess the role played by collagen bioscaffolds, together with explanted cells and growth factors examined during the in vitro studies, in the healing process by comparing teeth transplanted into an existing socket with those transplanted into a prepared site. 3. Evaluate the effect of growth factors, explanted cells and bioscaffolds on regeneration of tissues lost as a result of ligature-induced periodontal infection.Read moreRead less
Regulation Of Porphyromonas Gingivalis Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
Chronic periodontitis (gum disease) is a chronic inflammatory disease of the supporting tissues of the teeth associated with bacteria that results in the destruction of tooth support and can ultimately lead to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease. The bacterium Porphyromonas gingivalis is recognized as the major causative pathogen in the development of chronic periodontitis. ....Chronic periodontitis (gum disease) is a chronic inflammatory disease of the supporting tissues of the teeth associated with bacteria that results in the destruction of tooth support and can ultimately lead to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease. The bacterium Porphyromonas gingivalis is recognized as the major causative pathogen in the development of chronic periodontitis. This bacterium is part of subgingival dental plaque, a biofilm attached to the surface of the tooth below the gum line, and releases a range of proteins and cytotoxic agents that cause damage to the tooth's supporting tissues both directly and indirectly through the dysregulation of the host's immune response. To cause disease this bacterium must be able to grow as a biofilm and withstand the immune response of the host. Detailed knowledge of how this bacterium is able to establish and proliferate in subgingival plaque, tolerate the oxidative attack and elevated temperatures that are part of the immune response and obtain the essential micronutrient iron will provide new targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic for the control of chronic periodontitis. We will use a state of the art DNA microarray analysis to determine the proteins that regulate genes associated with the virulence of this bacterium. The insights we gain from this study will have broader application for the understanding of human disease that is caused by bacteria that grow as biofilms on various surfaces of the human body.Read moreRead less