Deciphering How TCR Affinity Regulates CD4 T Cell Help In Immunity And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$850,885.00
Summary
Immune responses require the coordinated interaction and cross-talk between two types of white blood cells known as CD4 and CD8 T cells. A dysregulated interaction between these cells could be the cause of autoimmune and persistent infections by pathogens leading to chronic diseases. The aim of this proposal is to provide a deeper understanding of CD4/CD8 T cell interactions to improve immune outcomes in many chronic diseases in which interaction between these two immune cells is critical.
A Unique Network Of Phagocytic Cells At The Interface Between The Liver And Peritoneal Cavity
Funder
National Health and Medical Research Council
Funding Amount
$787,521.00
Summary
This project aims to characterise the nature and ontogeny of a novel population of cells with phagocytic capacity that forms a network underlying the capsule of mouse and human liver reminiscent of that formed by Langherans cells in the epidermis of the skin. In this project we will characterise this newly described liver capsular macrophage subset, define their ontogeny and assess their specific functions.
Inflammatory Mediators Of Liver Injury In Chronic Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$349,336.00
Summary
Presently, liver disease from chronic hepatitis C and obesity represents a major health problem. Overall, approximately 50% of Australians with chronic hepatitis C are obese and these patients are at significantly increased risk of rapidly progressing to liver failure. It is now recognized that fat derived factors play an important role in regulating inflammatory responses. This grant proposal aims to gain insight into how liver and fat derived inflammatory factors interact to promote increased ....Presently, liver disease from chronic hepatitis C and obesity represents a major health problem. Overall, approximately 50% of Australians with chronic hepatitis C are obese and these patients are at significantly increased risk of rapidly progressing to liver failure. It is now recognized that fat derived factors play an important role in regulating inflammatory responses. This grant proposal aims to gain insight into how liver and fat derived inflammatory factors interact to promote increased liver damage in chronic hepatitis C and obesity.Read moreRead less
The Clinical Utility Of Small Airway Function Tests In Paediatric Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Respiratory disease is an important child health issue with long term implications into adulthood. The evaluation of small airways involvement in disease processes, using an accurate sensitive measures of function, such as forced oscillation technique and multiple breath washout, potentially facilitates not only early detection of disease, but instigation of earlier treatment, better assessment of response to treatment, and ultimately better outcome.
Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date
Metabolically Reprogramming The Stroma To Starve Pancreatic Tumours
Funder
National Health and Medical Research Council
Funding Amount
$598,848.00
Summary
Pancreatic cancer claims five Australian lives every day. Despite aggressive treatment regimes, there has been no improvement in patient survival in the last decade. Evidence suggests that targeting cancer cells alone is not enough. Pancreatic tumours are surrounded by an extensive scar tissue reaction (stroma). This intense stromal reaction inhibits drug delivery and increases tumour growth. Thus, decreasing the stroma is a potential therapeutic strategy and is the focus of this proposal.
The Unique Nature Of Gamma Delta T Cell Recognition Resolved Through Interaction With H2-Q10
Funder
National Health and Medical Research Council
Funding Amount
$699,031.00
Summary
The liver is important for both digestion and immunity. Given these opposing functions, the liver must exert control points that prevent the immune system from recognising food products. We have now identified a new molecular target that controls the development of immune cells in the liver.
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
EPITHELIAL ION TRANSPORT DEFECTS IN CYSTIC FIBROSIS: PATHOPHYSIOLOGY AND TREATMENT
Funder
National Health and Medical Research Council
Funding Amount
$290,440.00
Summary
The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease a ....The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, altered salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airway with repeated bacterial infections damaging the lungs. Simple tests have been designed to directly measure the movement of salt across the surface of the nasal passage using a fine soft rubber tube. Movement of mucous in the nose is measured using other simple techniques that are currently used diagnostically. Together, these tests in the nose provide vital information about how the surface of normal human airway moves salt, water and mucous. Any differences found in CF patients will then give us a good idea of the problems found in the CF lung. We will study the interactions between calcium, sodium and chloride in the fluid lining the airways, measuring changes in salt and mucous movement. A range of testing procedures will be used in human volunteers, anaesthetised mice and isolated tissues from sheep. We have already demonstrated important links between the fluid lining the airways and salt movement, and we expect that this may lead to the development of new treatments for Cystic Fibrosis. This therapy will focus on treating the lung problems of CF patients, the major cause of disability. We anticipate that this preventative therapy may offer real benefits in the fight to cure CF.Read moreRead less