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.
Molecular Profiling Of The Immunoglobulin Proteome In Primary Sjögren’s Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$322,460.00
Summary
Primary Sjögren’s syndrome is a common autoimmune disease. The patients have high levels of circulating immunoglobulins (Igs) in their blood-a hallmark of the disorder. The applicant proposes to sequence these Igs and identify their so-called variable region molecular signatures. These signatures can then be used in a mass spectrometric-based diagnostic platform to identify unique clones in patients as early markers of the disease process, and hopefully lead to more relevant diagnostic markers.
Identification Of The Conformation Dependant Targets Of Autoimmune Disease Linked Variation In Human Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,001,815.00
Summary
Specialised immune cells called regulatory T cells act as the policemen of the immune system, preventing the immune system attacking itself, but still fighting infections. If these cells do not work properly, autoimmune diseases such as type 1 diabetes or IBD can arise, because of immune attack on normal body tissue by mistake. In order to explain how this goes wrong we need to carefully identify all of the gene interactions in these cells including interactions over long distances in the DNA.
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
Breathing disturbances and reflexes in sleep and effects on sleep and daytime function. This project will investigate protective reflexes in sleep and the impact of breathing disturbances and frequent arousal on markers of brain functioning and health. This will also significantly advance the understanding of key mechanisms promoting unstable breathing in sleep and ill health and functioning from disturbed sleep.
Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount ....Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount before we can understand and develop treatments for dealing with heart problems. This information will facilitate the development of techniques to treat and prevent heart rhythm disorders that are a common cause of morbidity in the community.Read moreRead less
Functional characterisation of poly-histidine triad proteins. This project aims to understand the role and function of a novel family of surface proteins produced by Streptococci. These so-called polyhistidine triad proteins are known to contribute to capacity to cause disease in animals and humans, but we need to know how they work, as they may be excellent targets for novel drugs or vaccines.
Novel perspectives on the function of AB5 toxin B subunits in pathogenic bacterial. AB5 toxins are produced by bacteria that cause important diseases in humans and livestock. This project tests the hypothesis that the components of the toxins responsible for binding to host cells and tissues also directly contribute to cellular damage, thereby providing a better understanding of how AB5 toxin-producing bacteria cause disease.
Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard ....Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard tail), to describe the regrowth process and determine the abundance, location, functional properties and molecular control of the new lymphatics. Furthermore, if reptilian lymphatic growth factors can promote lymphangiogenesis in mammals, we can design novel therapeutic approaches using reptilian ligands to promote lymphangiogenesis in lymphoedematous human tissues.Read moreRead less