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
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.
Flaviviral Proteases As Viable Targets For Antiinfective Drugs
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Viruses hijack the machinery and nutrients of cells they infect in order to reproduce. We will study viral enzymes (proteases) essential for virus replication, use fluorescent probes to learn where the viral enzymes hide and act in infected cells, track the passage of drugs aimed at these enzymes, design drugs to block their actions and stop virus replication, and test antiviral activity against Dengue, West Nile, Japanese Encephalitis and Yellow Fever viruses which infect millions of people.
Disarming Deadly Viruses: High Throughput Protease Screening Using Massive Peptide Libraries
Funder
National Health and Medical Research Council
Funding Amount
$405,625.00
Summary
Viral diseases affect millions of people worldwide with mortality rates as high as 50%. Viral enzymes help liberate proteins essential for viral replication. The rapid identification of the activity and specificity of these viral enzymes is important to combat outbreaks of viral disease and has become possible through biomedical device technology developed by the industry partner. With just 17 new drugs approved by the FDA in 2002, the proposed program has the potential to deliver new drugs quic ....Viral diseases affect millions of people worldwide with mortality rates as high as 50%. Viral enzymes help liberate proteins essential for viral replication. The rapid identification of the activity and specificity of these viral enzymes is important to combat outbreaks of viral disease and has become possible through biomedical device technology developed by the industry partner. With just 17 new drugs approved by the FDA in 2002, the proposed program has the potential to deliver new drugs quickly and efficiently, and this will be of benefit to viral disease sufferers worldwide.Read moreRead less
Disruption Of Proteolytic Cascades In The Skin:towards Halting The Atopic March
Funder
National Health and Medical Research Council
Funding Amount
$388,601.00
Summary
There are over 3000 named skin disorders which range in severity from the trivial including acne, to life threatening such as skin cancer. Many skin diseases result from a lack of control over the way the skin maintains itself. Cutting the connections that hold cells together is key to balancing loss of skin cells with their continuous replacement. This project focuses on making compounds to block skin cell shedding with the longer term aim of producing novel drugs to treat skin disease.
Control Of Proteases In Infectious, Degenerative And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$11,668,789.00
Summary
Proteases are enzymes that control key processes in humans. The research in this program will result in major discoveries in the field of proteases and their inhibitors, with a focus on inflammatory, cardiovascular and degenerative disease. The knowledge gained from this strong foundation of fundamental research will underpin the translational outcomes necessary to combat the debilitating effects of immunological dysfunction, conformational and cardiovascular disease.
Understanding The Role Of Cell Death In Blood Vessel Regression And Regrowth
Funder
National Health and Medical Research Council
Funding Amount
$468,059.00
Summary
Blood vessels are essential to distribute oxygen and nutrients throughout our bodies, and as such, disruptions to normal blood vessel behaviour can have significant impacts on health. This research is aimed at understanding how blood vessel networks can regrow after damage in order to maintain healthy blood supply to a tissue. This work will be particularly relevant to diseases where blood vessel loss or inappropriate blood vessel growth occur.