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
Role Of Regulatory Genes In The Control Of Toxin Production In Clostridium Perfringens
Funder
National Health and Medical Research Council
Funding Amount
$495,710.00
Summary
This project investigates how the bacteria responsible for gas gangrene, an often fatal wound infection, control or regulate the expression of genes that encode toxins and other virulence factors. The overall objective is to develop a detailed understanding of the function and biological role of each element in these regulatory systems, thereby making a major contribution to our knowledge of how bacteria control the production of toxic products that are essential for the disease process.
DIREKT: Disarming The Intravascular Innate Immune Response To Improve Modalities For Chronic Kidney Disease Treatment
Funder
National Health and Medical Research Council
Funding Amount
$362,830.00
Summary
Dialysis is the mainstay treatment for patients with end-stage kidney disease while they await transplantation. However, the dialysis process causes inflammation in patients, affecting their health and longevity. This project aims to develop new bioreagents that can be applied to dialysis devices to reduce inflammation and thus improve patient outcomes. These bioreagents will also be used to modify donor kidneys so that they are protected from inflammation associated with transplantation.
The Role Of Transcriptional Co-activators And Co-repressors During Embryonic Development
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
Every creature starts out as a single fertilized egg. The genome directs the embryonic development of the egg by regulating the expression of genes each of which must be turned on or off at the correct time and place. This essential balance between the activation or repression of genes is controlled by groups of proteins, including ‘transcriptional co-activators’ and ‘repressors’. This project aims to better understand the role of these proteins during embryonic development.
E2F Inhibitors As Anticancer Agents For Squamous Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Squamous cell carcinoma of the head and neck is one of the six most frequent causes of cancer death worldwide. these tumours are currently treated with surgery, radiotherapy and chemotherapy. Although these treatments are associated with a five year survival rate of between 40% and 60% there is a critical need for more effective and less destructive treatments. In this application we will extend on our earlier work in which we identified the protein E2F1 as being a major contributor to tumour de ....Squamous cell carcinoma of the head and neck is one of the six most frequent causes of cancer death worldwide. these tumours are currently treated with surgery, radiotherapy and chemotherapy. Although these treatments are associated with a five year survival rate of between 40% and 60% there is a critical need for more effective and less destructive treatments. In this application we will extend on our earlier work in which we identified the protein E2F1 as being a major contributor to tumour development. In normal cells, E2F1 is required for the regulated growth of head and neck cells. However, we found that in head and neck tumours, E2F1 is overactive and contributes to the dergulated growth of the tumour. In this project we will test our newly developed inhibitors of E2F1 on various tumour cells derived from head and neck cancers to see how effective they are at stopping tumour cell growth. Furthermore we will test these compounds in animal models of head and neck cancer to determine whether they will be useful therapeutic agents for treatment of human cancer. Early results on tumour cell lines look very promising.Read moreRead less