The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. In this project, we make use of special microscopes to examine the glomerulus during an inflammatory response, with the aim of understanding the actions of leukocytes present in glomeruli and how they cause inflammation and damage the glomerulus.
Regulation Of Leukocyte Recruitment In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$686,656.00
Summary
In inflammatory diseases such as asthma, arthritis and atherosclerosis, white blood cells enter affected tissues causing inflammation and tissue destruction. This research will investigate the processes whereby white blood cells enter affected tissues, particularly how they exit the circulation, and migrate throughout tissues during inflammatory responses. An improved understanding of this process may identify new ways of interfering with the disease process in various inflammatory diseases.
Role Of Tetraspanins In Integrin Function And Leukocyte Migration
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Cell migration is a very important component of the immune system. White blood cells, migrate from tissues to lymph nodes to initiate immune responses, and can migrate from blood to sites of inflammation to fight infection. This grant studies a type of protein called a tetraspanin that we believe controls white blood cell migration. Understanding the precise role of tetraspanins in this process will further our understanding of inflammation in disease processes.
A Novel Mechanism For The Regulation Of T Cell Shape And Function.
Funder
National Health and Medical Research Council
Funding Amount
$384,398.00
Summary
T cells are a key component of the immune system, and an understanding of their regulation has already lead to important therapeutic interventions. It is now apparent that the shape of the T cell impacts upon its ability to be activated, to migrate through the body, and to kill target cells. We have identified a novel means by which T cell shape is controlled, involving a group of proteins which orchestrate molecular traffic throughout the cell. This project application is to elucidate the mecha ....T cells are a key component of the immune system, and an understanding of their regulation has already lead to important therapeutic interventions. It is now apparent that the shape of the T cell impacts upon its ability to be activated, to migrate through the body, and to kill target cells. We have identified a novel means by which T cell shape is controlled, involving a group of proteins which orchestrate molecular traffic throughout the cell. This project application is to elucidate the mechanisms by which the group of proteins regulates T cell shape and function. We will test whether the proteins act together to integrate signals throughout the entire T cell, and will test whether the proteins influence T cell function in the test tube and in the mouse.Read moreRead less
Molecular Dissection Of Cytokine-mediated Regulation Of Human B-cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$119,314.00
Summary
Interleukin 21 is a molecule which activates B cells. Defects in this pathway cause immunodeficiency where individuals cannot make antibodies, while constant activation has been reported in mouse models of autoimmunity. Examining these pathways will shed light on the causes of human immune disease, and may reveal molecules that could be targeted for the treatment of immunodeficiency and autoimmunity. Amplification of normal immune responses could lead to the development of improved vaccines.
Competition For Polarity Influences Lymphocyte Differentiation And Function
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
CD46 is a protein on human cells that viruses and bacteria bind to during infection. Our laboratory has found that binding of CD46 on immune cells impairs their ability to recognize and kill target cells and may explain the immunosuppression caused by measles infection. We aim to investigate the mechanisms behind the effect of CD46 on immune cells. The outcomes of this study will define new paradigms in lymphocyte biology and determine how CD46 influences the immune response to infection.
The Interaction Between CD46 And PSD-95/Dlg-4: Roles In Cell Polarisation And CD46 Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$70,000.00
Summary
Immune defence against pathogens is primarily achieved by the activities of a range of blood cells, including T cells. T cells have specialised functions involving direct killing of the pathogen, and recruitment and activation of other immune cells. Many of these functions require the lymphocyte to become polarised, or asymmetric, in order to concentrate the appropriate cellular machinery towards the site of activity. Examples of polarisation in lymphocytes includes (i) the formation of a single ....Immune defence against pathogens is primarily achieved by the activities of a range of blood cells, including T cells. T cells have specialised functions involving direct killing of the pathogen, and recruitment and activation of other immune cells. Many of these functions require the lymphocyte to become polarised, or asymmetric, in order to concentrate the appropriate cellular machinery towards the site of activity. Examples of polarisation in lymphocytes includes (i) the formation of a single protrusion, or uropod, that forms the basis for cell-cell interactions, (ii) the formation of an immune synapse which allows a T cell to recognise a pathogen, and (iii) the direction of the cellular killing machinery towards the target. The process of cell polarisation is best characterised in neurons and epithelial cells, both of which are asymmetric. In each cell type, a major mechanism of regulating polarisation is the expression and targeting of a family of proteins containing regions called PDZ domains. PDZ domains mediate protein-protein interactions and so allow the assembly of large molecular scaffolds which hold proteins in specific cell sites. The loss of cell polarity in some cells is thought to cause uncontrolled proliferation and tumour progression, and some of the PDZ-containing proteins are tumour suppressors. We have identified a PDZ-containing protein that is polarised in T cells, and have evidence that this protein interacts with and controls the polarisation of a cell surface receptor whose functions include the regulation of T cell function and proliferation. The aim of this proposal is to determine the mechanisms and functional consequences of polarisation of these two proteins in T cells, and to determine whether their interaction or polarisation is important for T cell proliferation.Read moreRead less
Immune defence against pathogens is primarily achieved by the activities of a range of blood cells, including T cells. T cells have specialised functions involving direct killing of the pathogen, and recruitment and activation of other immune cells. Many of these functions require the lymphocyte to become polarised, or asymmetric, in order to concentrate the appropriate cellular machinery towards the site of activity. Examples of polarisation in lymphocytes includes (i) the formation of a single ....Immune defence against pathogens is primarily achieved by the activities of a range of blood cells, including T cells. T cells have specialised functions involving direct killing of the pathogen, and recruitment and activation of other immune cells. Many of these functions require the lymphocyte to become polarised, or asymmetric, in order to concentrate the appropriate cellular machinery towards the site of activity. Examples of polarisation in lymphocytes includes (i) the formation of a single protrusion, or uropod, that forms the basis for cell-cell interactions, (ii) the formation of an immune synapse which allows a T cell to recognise a pathogen, and (iii) the direction of the cellular killing machinery towards the target. The process of cell polarisation is best characterised in neurons and epithelial cells, both of which are asymmetric. In each cell type, a major mechanism of regulating polarisation is the expression and targeting of a family of proteins containing regions called PDZ domains. PDZ domains mediate protein-protein interactions and so allow the assembly of large molecular scaffolds which hold proteins in specific cell sites. The loss of cell polarity in some cells is thought to cause uncontrolled proliferation and tumour progression, and some of the PDZ-containing proteins are tumour suppressors. We have identified a PDZ-containing protein that is polarised in T cells, and have evidence that this protein interacts with and controls the polarisation of a cell surface receptor whose functions include the regulation of T cell function and proliferation. The aim of this proposal is to determine the mechanisms and functional consequences of polarisation of these two proteins in T cells, and to determine whether their interaction or polarisation is important for T cell proliferation.Read moreRead less