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
Identification Of Porphyromonas Gingivalis Genes Required For Iron/haem Acquisition And Biofilm Formation
Funder
National Health and Medical Research Council
Funding Amount
$476,836.00
Summary
Periodontal diseases are some of the most common bacterial diseases of humans and along with dental caries, account for approximately 90% of all tooth loss in the Australian population. A recent survey of oral health in Australia found that in the 30-34 age group over 20% of people had moderate to severe periodontal disease, indicating that periodontitis is a major public health problem. Specific bacteria, especially Porphyromonas gingivalis, that grow as bacterial biofilms (dental plaque) cause ....Periodontal diseases are some of the most common bacterial diseases of humans and along with dental caries, account for approximately 90% of all tooth loss in the Australian population. A recent survey of oral health in Australia found that in the 30-34 age group over 20% of people had moderate to severe periodontal disease, indicating that periodontitis is a major public health problem. Specific bacteria, especially Porphyromonas gingivalis, that grow as bacterial biofilms (dental plaque) cause periodontal disease. In this study we will utilise the latest technology available to determine which genes of the bacterium are important for biofilm growth, iron acquisition and virulence in an animal model. We will investigate how the bacterium acquires iron, as there is usually little available iron for bacterial growth on human tissues and the ability of the bacterium to free itself from this iron limitation is associated with pathogenicity. The determination of the role of iron availability in biofilm formation and virulence of the bacterium will help us to understand the changes that occur in the initiation of disease and may allow the development of early intervention strategies. The significance of this work is that we will gain an understanding of how this bacterium functions as an opportunistic human pathogen. We will determine which genes are essential for growth as a biofilm and to produce disease in an animal model. This will enable the development of therapeutic and prophylactic interventions targeted to specific bacterial gene products required to produce disease.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
Generation Of Induced Pluripotent Stem (iPS) Cells And Their Potential Use In Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$798,350.00
Summary
Dental diseases affecting the gums (periodontal diseases) are extremely prevalent. 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 propose to generate induced pluripotent stem cells from gums and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.
This proposal aims to examine how the oral bacterial pathogen, P.gingivalis, interacts with the host to worsen the severity of disease in rheumatoid arthritis. We propose a new mechanism whereby the pathogen directly activates a major destructive host pathway to promote tissue and bone destruction, which are two of the clinical hallmarks of rheumatoid arthritis. We also propose that this host-pathogen interaction occurs in periodontal disease.
Complement Inhibitors For Treatment Of Chronic Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$623,606.00
Summary
We aim to provide new therapeutic approaches to gum disease, which not only causes tooth loss, but also contributes to other diseases, such as cardiovascular disease and diabetes. We will find new methods to inhibit a system in our own bodies that contributes to inflammation and gum disease and test the effects of these methods of inhibition in disease models. In this way, we hope to lessen the burden of gum disease on the Australian population.
Structural Role Of The Host Cytoskeleton During Invasion Of Intracellular Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
During infection by bacteria, the 'skeleton' of cells plays critical roles in sensing the invading germs and destroying them. To counteract this, bacteria have evolved strategies to hijack the cell skeleton to promote their own survival, and spread. This intriguing molecular arms race is continuously co-evolving. Understanding this process in great details will have the potential to design novel therapeutics to counteract bacterial and viral infections.
Combating Infectious Diseases By Harnessing Macrophage Functions
Funder
National Health and Medical Research Council
Funding Amount
$688,152.00
Summary
Infectious diseases present a persistent global health threat. For patients with life-threatening diseases caused by bacterial pathogens, antibiotics provide the last resort. Antibiotic resistance, even for newly developed antibiotics, is widespread within the bacterial community. New strategies are urgently needed to combat most bacterial infections. This proposal will investigate a new strategy to train and boost our immune systems to combat infectious diseases.
Cementogenesis And New Periodontal Attachment Formation Using Cell Sheets
Funder
National Health and Medical Research Council
Funding Amount
$483,787.00
Summary
Periodontitis, a chronic inflammatory disease, affects 30-40% of the population and is a leading cause of soft and hard tissue destruction around teeth and tooth loss. Current treatment does not regenerate lost tissues resulting in inferior aesthetics and function. By using oral tissue engineered in the laboratory capable of supporting the growth and differentiation of cells necessary to achieve regeneration, the original structure and function of previously destroyed tissue may be restored.
Associations Between Periodontal Disease And Cardiovascular Surrogate Endpoints In An Adult Indigenous Population
Funder
National Health and Medical Research Council
Funding Amount
$1,346,328.00
Summary
The relationship between periodontal disease and cardiovascular surrogate endpoints, both of which are high among the Indigenous Australian population, is established. This study seeks to explore the prevalence of cardiovascular surrogate endpoints among this population with periodontal disease, and to determine if implementation of a periodontal intervention leads to improved cardiovascular risk outcomes. There may be benefit in applying this model to other areas of Indigenous health research.