Structure And Biosynthesis Of Entamoeba Histolytica Proteophosphoglycans
Funder
National Health and Medical Research Council
Funding Amount
$85,380.00
Summary
The intestinal parasite, Entamoeba histolytica is the cause of amoebic dysentry and liver abscess. It is the second most important parasitic disease after malaria, infecting 50 million people and causing 110 000 deaths annually. We have recently shown that the cell surface of infective stages of this parasite are coated by an unusual class of macromolecules called proteophosphoglycans (PPGs). These molecules appear to be major virulence factors, and the expression of PPGs with particular sugar m ....The intestinal parasite, Entamoeba histolytica is the cause of amoebic dysentry and liver abscess. It is the second most important parasitic disease after malaria, infecting 50 million people and causing 110 000 deaths annually. We have recently shown that the cell surface of infective stages of this parasite are coated by an unusual class of macromolecules called proteophosphoglycans (PPGs). These molecules appear to be major virulence factors, and the expression of PPGs with particular sugar modifications is associated with highly pathogenic strains. This proposal aims to determine the precise structure of the PPGs and to define functionally important domains in these molecules. We will also investigate how these molecules are assembled and processed in the parasite. In particular, we aim to characterize enzymes that generate PPG structures only found in virulent strains of Entamoeba histolytica. Assays will be established for these enzymes which will allow us to screen for inhibitors that may be used as potential anti-amoebic drugs. These studies will provide insights into the surface chemistry of these important human parasites and identify new drug targets.Read moreRead less
Cholestasis And Hepatocyte Injury In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$615,967.00
Summary
The aim of this project is to understand the consequences of long-term cholestasis or impaired bile excretion/flow on normal liver cells (hepatocytes) and to test whether specific bile acids can cause irreversible damage to hepatocytes leading to their transformation into pre-malignant cells and hepatocellular carcinoma (primary liver cancer). The results from this project will inform new strategies in screening, prevention and treatment of liver cancer in children and adults with cholestasis.
Significance Of Microparticles In The Pathogenesis Of Liver Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$643,958.00
Summary
The overall aim of the project is to investigate the significance of microparticles in liver ischemia reperfusion injury (IRI). IRI causes damage to donor livers stored in preparation for liver transplantation. We postulate that microparticles released from the liver are critical in this form of injury. The expected outcomes are novel insights into liver IRI with the aim of developing new approaches to prevent liver damage during liver surgery, transplantation and shock.
The Role Of MBOAT7 In Hepatic Inflammation: Implications For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$848,340.00
Summary
When a fatty liver progresses to develop inflammation, patients are at-risk of liver-related morbidity and death. Currently, there are no effective therapies. From human studies, we have discovered that a lipid modifying enzyme (MBOAT7) profoundly regulates liver inflammation. In this proposal, we will obtain a detailed understanding of how the activity of this pathway modulates inflammation. We expect to show that MBOAT7 is a novel ‘druggable’ pathway for the treatment of liver inflammation.
P53 And Hepatocyte Proliferation In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$331,360.00
Summary
The aim of this project is understand how loss of control of p53, a tumour suppressor gene, in liver cells causes the transformation of normal liver cell (hepatocyte) to ‘rouge’ pre-cancerous cells in hepatocellular carcinoma (HCC) or primary liver cancer. We will test novel therapies to restore p53 function in liver cells in order to prevent or retard the development of HCC in patients with cirrhosis and those ‘at risk’ of this rapidly increasing fatal cancer in Australia.
MERTK Receptor Tyrosine Kinase: A Novel Therapeutic Target For Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$870,972.00
Summary
Hepatic fibrosis is the principal cause of liver-related morbidity and mortality, for which there are no effective therapies. Thus, there is an urgent and unmet need to identify new targets to treat liver fibrosis. We have demonstrated for the first time, that liver fibrosis correlates with elevated hepatic expression of MERTK, a receptor tyrosine kinase. This project will explore whether MERTK function can be exploited to target and reverse liver fibrosis
The Role Of The Hepatocyte And EMMPRIN In Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$607,487.00
Summary
This research plan investigates the role of the hepatocyte, the principal functional cell within the liver in the development of liver disease. Liver injury can result in end-stage scaring known as cirrhosis as well as leading to liver cancer. Our research aims to identify strategies for reversing the fibrotic process and result damage to the liver