Characterization Of A Novel Secretion And Attachment System Necessary For The Formation Of A Virulence Coat In Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$828,857.00
Summary
In this study we will characterize a novel bacterial secretion system that we have discovered. This system mediates the secretion of proteins from the bacterial cell and their attachment to the cell surface. This system is essential for the virulence of a bacterium associated with severe gum disease. The chacterization of this system may offer opportunities for the development of new treatments to target this disease.
The Role Of Porphyromonas Gingivalis Outer Membrane Vesicle Biogenesis In Virulence And Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$734,288.00
Summary
Porphyromonas gingivalis is a keystone pathogen in chronic periodontitis. This bacterium exists as part of a biofilm on the surface of the tooth and selectively packages enzymes, toxins and antigens on to vesicles that penetrate host tissue and cause the inflammatory response that is associated with disease progression. In this study we will determine the host response to vesicles and determine the role of a specific protein in vesicle biogenesis.
To Biochemically Trick P-Glycoprotein (Pgp) To Target Resistance Via Lysosomal Pgp
Funder
National Health and Medical Research Council
Funding Amount
$603,848.00
Summary
We have discovered an innovative biochemical strategy whereby our novel compounds exploit and trick a part of the detoxification machinery, that is the transporter, P-glycoprotein, to specifically kill drug resistant cancer cells. Herein, we take advantage of this biochemical mechanism to design novel and safe drugs to selectively target resistant tumours.
Microparticles And Selective Trait Dominance In Multidrug Resistant Cancers
Funder
National Health and Medical Research Council
Funding Amount
$478,115.00
Summary
Multidrug resistance (MDR) is the cause of treatment failure in 90% of patients with metastatic cancer. We recently discovered a novel resistance mechanism in which microparticles provide a vehicle for intercellular transfer of MDR. We now report that MP play an even more significant role in conferring MDR, by the ñre-templatingî of cancer cell traits. This has considerable potential for translation into clinical outcomes with the identification of alternative drug targets and therapeutics for t ....Multidrug resistance (MDR) is the cause of treatment failure in 90% of patients with metastatic cancer. We recently discovered a novel resistance mechanism in which microparticles provide a vehicle for intercellular transfer of MDR. We now report that MP play an even more significant role in conferring MDR, by the ñre-templatingî of cancer cell traits. This has considerable potential for translation into clinical outcomes with the identification of alternative drug targets and therapeutics for the circumvention of MDR clinically.Read moreRead less
A Mechanistic Approach To Therapy Development For Chronic Traumatic Encephalopathy Using Small And Large Animal Models Of Concussion
Funder
National Health and Medical Research Council
Funding Amount
$492,844.00
Summary
Repeated concussion in athletes has recently been associated with the development of a neurodegenerative disorder known as chronic traumatic encephalopathy (CTE). While the neuropathology seems to be well characterised, the mechanisms associated with CTE development are not. This proposal will demonstrate that mechanically induced release of the neurotransmitter substance P accounts for much of the neuropathology in CTE, and will develop a novel therapy that will prevent such development.
Understanding Multidrug Resistance In Cancer: Identification Of The Substrate And Inhibitor Binding Sites In P-glycoprotein
Funder
National Health and Medical Research Council
Funding Amount
$284,343.00
Summary
Cancers expressing the multidrug transporter P-glycoprotein (P-gp) are resistant to chemotherapy. The clinical impact of P-gp is so large that the National Cancer Institute (USA) “profiles” all anticancer drugs for transport by P-gp, primarily because the mechanism of drug binding and transport by P-gp is unknown. The aim of this proposal is to understand the molecular details of how drugs bind to and interact with P-gp, a major step in our understanding of P-gp mediated chemotherapy resistance.