How Does Dietary Cholesterol Induce Non-alcoholic Steatohepatitis?
Funder
National Health and Medical Research Council
Funding Amount
$802,600.00
Summary
Non-alcoholic fatty liver disease is the most common liver disease that can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Dietary cholesterol is a major risk factor for NASH. We can demonstrate that cholesterol changes the gut bacteria. These bacteria generate toxic chemicals (bile acids) that signal to the liver and induce NASH. In this project, we use novel ways to clarify the mechanisms of liver inflammation and test novel therapeutic approaches to reverse it.
Hepatitis C affects a quarter of a million Australians, causing insidious but progressive liver disease which culminates in liver failure or cancer. There is no vaccine and prevention programs have limited effectiveness, but new antiviral therapies now offer high rates of cure. This Program will evaluate strategies to improve the health of those affected and prevent new infections by better understanding of the virus and the body’s immune response, including scarring and liver cancer formation.
Imaging The Hepatitis C Virus Life Cycle In Real-time
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may unco ....Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may uncover novel therapeutic strategies to combat HCV.Read moreRead less
Understanding How GATA2 Controls Lymphatic Vessel Valve Development
Funder
National Health and Medical Research Council
Funding Amount
$697,942.00
Summary
Mutations in the GATA2 gene cause human lymphoedema as a result of the crucial role that GATA2 plays in controlling the expression of genes important for building functional lymphatic vessels. Here we aim to gain a complete picture of the cellular and molecular events that are controlled by GATA2 in lymphatic vessels and in particular, in lymphatic vessel valves.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Transplantation of pancreatic islets is the only cure for type 1 diabetes (T1D). Unfortunately, many of the transplanted islet cells die quickly due to an inadequate supply of blood. Herein, we investigate a novel cell surface protein for its role in islet and blood vessel survival and function. Furthermore, we use nanotechnology to provide said protein to the islet cells during transplantation for increased survival and function. Ultimately, this work may cure more patients with diabetes.
Histone Demethylase KDM6A Is A Novel Target For Treating Craniosynostosis In Children With Saethre-Chotzen Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$548,854.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fused coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting this key molecular regulator with chemical inhibitors will help prevent the premature fusion of cranial sutures.
Tyrosine Kinase Receptor C-ros-oncogene 1 Mediates Twist-1 Haploinsufficiency Induced Craniosynostosis In Children: A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$562,863.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fussed coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting these key molecular signalling components with chemical inhibitors will help prevent the premature fusion of cranial sutures.
The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.
MicroRNAs are small molecules that modulate the expression of most genes and so affect nearly every biological process and pathology although, they were only discovered in humans less than 10 years ago. The bottleneck in discovering the functions of miRNAs is in identifying their molecular targets, the majority of which remain unknown. We aim to comprehensively identify direct target genes of epithelial-specific microRNAs and to confirm a number of them by gene target validation approaches.