Fine Positioning And Effector Function Of T Cells Recruited To The HCV Infected Liver
Funder
National Health and Medical Research Council
Funding Amount
$321,973.00
Summary
The majority of patients who become infected with hepatitis C virus (HCV) are unable to mount an effective immune response and clear the virus and therefore develop lifelong (chronic) infection. The persistence of virus in the liver of patients with chronic infection results in the recruitment of significant numbers of immune cells, notably T cells, from the bloodstream into the liver where they are involved in both viral control (but not viral clearance) and liver injury. The level of tissue in ....The majority of patients who become infected with hepatitis C virus (HCV) are unable to mount an effective immune response and clear the virus and therefore develop lifelong (chronic) infection. The persistence of virus in the liver of patients with chronic infection results in the recruitment of significant numbers of immune cells, notably T cells, from the bloodstream into the liver where they are involved in both viral control (but not viral clearance) and liver injury. The level of tissue injury observed and the speed of disease progression may be linked to the type of T cells recruited, their function, and their position in the liver. The aims of this project are to determine the factors involved in the fine positioning of T cells in the liver and establish a relationship between T cell recruitment, function, and progression of HCV disease in the liver.Read moreRead less
What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.
Proatherogenic CD4 NKT Cells And Atherosclerosis: Molecular Mechanisms And Therapeutic Strategies For Suppression
Funder
National Health and Medical Research Council
Funding Amount
$504,348.00
Summary
Immune cells called CD4+ iNKT cells are known to be activated by lipids which initiate development of atherosclerosis, a disorder of blood vessels which is responsible for most heart attacks and strokes. We aim to investigate how these cells contribute to the development of this important blood vessel disoder and examine potential ways of inhibiting their activation to prevent heart attacks and strokes.
Regulation Of Cytokine Signalling: Structure And Biophysical Characterisation Of Key Protiens
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
Cells are informed when to grow, divide, migrate or die by protein molecules called cytokines. The cellular response to cytokines needs to be carefully regulated or else inflammation and other disorders will result. The SOCS (Suppressors Of Cytokine Signalling) family of proteins are a major regulator of cytokine signalling. This work will examine the structure and interactions of this important protein class.
Developmental-associated Dysregulation Of Innate Anti-microbial Immunity In Early Life As A Determinant Of Susceptibility To Atopic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
Previous NHMRC-sponsored research from the applicants has demonstrated that one of the strongest risk factors for subsequent development of asthma is having chest infections during infancy that are so severe that they trigger symptoms of fever and wheeze. It is not known what predisposes susceptible infants to these severe infections, and this project will attempt to define the mechanisms of susceptibility.
Protease Activated Receptor 2 Antagonist In Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,347.00
Summary
The immune response to infection involves a network of proteins that produce an inflammatory response. Sometimes this response is prolonged or uncontrolled and can lead to a large number of inflammatory and other diseases. We have discovered a class of drugs that can bind to a particular protein on the surface of human cells and control this inflammatory response. This property has the potential to treat a wide range of inflammatory and other diseases in humans.
THE ROLE OF THE HEPATOCYTE HEDGEHOG PATHWAY IN PROGRESSIVE LIVER INJURY
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
This research plan investigates the role of a pathway, known as the Hedgehog pathway, in the development of liver disease which can result in end-stage scarring known as cirrhosis and even lead to liver cancer (known as Hepatocellular carcinoma). Hepatocellular carcinoma is the globally the third most common cause of cancer death and our research will help to better understand how liver injury develops and how this then leads to liver cancer.
Monomeric C-reactive Protein As Pathogenic Factor And Therapeutic Target In Athero-thrombotic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$86,570.00
Summary
Vascular disease of the heart, brain and limbs affects many people in Australia and throughout the world. Current treatments assist in slowing the development and progression of established disease, but new developments are required. This project will investigate the role of C-reactive protein in vascular disease and evaluate its potential as a new therapeutic target in the future.
Discovery And Characterisation Of Novel Tick Evasins As Inhibitors Of Chemokine-mediated Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$654,847.00
Summary
An important aspect of inflammatory diseases is the migration of white blood cells into the affected tissues. This is controlled by a group of proteins called chemokines. Ticks, which live on mammalian hosts, produce proteins called evasins, which interact with host chemokines and thereby prevent inflammatory responses. This project will discover new tick evasins, study their chemokine interactions and investigate their ability to block inflammation in allergic asthma.
Towards Selective Targeting Of HDACs For Anti-inflammatory Applications
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
HDAC inhibitors are anti-cancer drugs that kill rapidly growing cells (like cancer cells). These drugs also have anti-inflammatory properties and so may be beneficial in chronic inflammatory diseases such as as Rheumatoid Arthritis. However, it is unknown how they reduce inflammation. In this project we aim to understand how HDAC inhibitors act as anti-inflammatory agents and to design new HDAC inhibitors with reduced side effects for the treatment of inflammatory diseases.