Neuronal communication relies on the process of exocytosis by which neurons release a neurotransmitter. Exocytosis is critical for the simplest muscle movement to complex tasks such as learning and memory, and is altered in several neurodegenerative pathologies. We will investigate how the protein Munc18 controls exocytosis. This research will be important for understanding how neurons communicate in health and disease and will be relevant to other processes such as insulin release in diabetes.
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 Secretory Antibodies In Mucosal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
This proposal will address the role of the antibodies that are present in all secretions from the gut, the lungs, the eye and mouth in maintaining the health of the mucosal (ie mucous covered) tissues from which they originate. It has long been presumed that these antibodies stop bacteria and other pathogens adhering to the surface of mucosal tissues. Our preliminary findings suggest that they have another very important role in removing excess inflammatory material from beneath the lining of th ....This proposal will address the role of the antibodies that are present in all secretions from the gut, the lungs, the eye and mouth in maintaining the health of the mucosal (ie mucous covered) tissues from which they originate. It has long been presumed that these antibodies stop bacteria and other pathogens adhering to the surface of mucosal tissues. Our preliminary findings suggest that they have another very important role in removing excess inflammatory material from beneath the lining of the mucosal tissues, to prevent recognition of this material by the immune system. Such recognition could result in serious consequences both locally (ie. in the gut) and more distally eg. in the pnacreas leading to diabetes. As a consequence, we believe that these antibodies are fundamental to health. The research could have important ramifications for diseases resulting from immune responses against host tissues, so-called autoimmune diseases like diabetes.Read moreRead less
The Dengue Virus Glycoprotein NS1 Binds Cholesterol And Mediates Cellular Activation
Funder
National Health and Medical Research Council
Funding Amount
$632,029.00
Summary
Cholesterol has been shown to play a vital role in the life cycle of many viruses. This project will investigate the basis of dengue virus interaction with this important host molecule and along with investigations of how dengue is able to stimulate host cells, will provide new insights into the way these viruses cause severe disease. Findings from this study will also aid in the development of new drug strategies for dengue and related viruses such as West Nile virus.
The Preferential Release Of Young Insulin Secretory Granules.
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
The aim of this study is to investigate the cause of reduced glucose induced insulin secretion in type 2 diabetes. In pancreatic beta-cells, insulin is packaged and stored in secretory granules (SGs). Upon stimulation, these SGs deliver insulin to the bloodstream. It is known that insulin SGs exist in two functionally distinct pools; and one pool is preferentially secreted upon stimulation. How a cell can differentiate the two SG pools is unclear, and we will address this issue in this project.
Interactions Between Excretory-secretory Proteins Of The Carcinogenic Liver Fluke And Host Cells
Funder
National Health and Medical Research Council
Funding Amount
$489,122.00
Summary
Throughout East Asia, there is a strikingly high prevalence of cholangiocarcinoma (CCA - cancer of the bile ducts) in regions where the human liver fluke is endemic. How the parasite casues cancer is multi-factorial, but one suspected mechanism is via the secretion of parasite proteins that enter bile duct cells and cause them to proliferate. We aim to understand this process and ultimately develop new control strategies to reduce the prevalence or the infection and CCA.
MOLECULAR CELL BIOLOGICAL ANALYSIS OF CAVEOLIN SECRETION
Funder
National Health and Medical Research Council
Funding Amount
$536,657.00
Summary
Aggressive forms of prostate cancer are associated with the release of a protein, called caveolin, from the cancerous cells. Caveolin is normally embedded in the cell surface and drives the formation of microscopic pits termed caveolae. In this proposal we will investigate how caveolin is secreted with a long-term goal of preventing the secretion, or the action, of caveolin.
Regulation Of Secretion Of The Fungal Virulence Determinant, Phospholipase B
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted ....Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted by the disease-causing fungus, Cryptococcus neoformans, and that it is important in enabling the fungus to invade the host's cells and spread around the body from the lungs to the brain, where it can cause meningoencephalitis. PLB is also produced by other disease-causing fungi. The mechanism of PLB secretion is completely unknown. In this project we aim to determine the pathways involved in PLB secretion with the intention of exploiting steps unique to pathogenic fungi, for the future design of new anti-fungal drugs.Read moreRead less
Invasive fungal infections are a serious, escalating health issue. They cause severe disease with high death rates and are very costly to the health system. Current drugs often have suboptimal efficacy and cause side effects. New drugs are needed urgently. Many fungi, including the AIDS-related pathogen, Cryptococcus neoformans, secrete phospholipase B (Plbp) to facilitate infection. We will identify and investigate the Plbp secretion pathway as a novel anti-fungal drug target.