Upregulation Of Chemokine Receptor Expression And Function On CD4+ T Cells In Primary And Secondary Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
This research will begin to determine the significance of changes in the amount of recently-discovered proteins on the surface of cells called T lymphocytes. These cells control immune responses and move throughout the body to do this. Sometimes, they are activated inappropriately and cause diseases like asthma, arthritis and multiple sclerosis and other times they need assistance for activation (vaccination). It is therfore important to understand how the movement of these cells through the bod ....This research will begin to determine the significance of changes in the amount of recently-discovered proteins on the surface of cells called T lymphocytes. These cells control immune responses and move throughout the body to do this. Sometimes, they are activated inappropriately and cause diseases like asthma, arthritis and multiple sclerosis and other times they need assistance for activation (vaccination). It is therfore important to understand how the movement of these cells through the body is controlled. A better understanding of this process shuld allow us to design better ways to control it, thereby controlling the negative aspects of T lymphocyte activation.Read moreRead less
Regulation Of The Anti-tumour Immune Response By The Chemokine Decoy Receptor CCX-CKR
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Melanoma is a significant cause of cancer-related deaths in Australians. Death is usually due to metastasis of the cancer to the lungs and other organs. In this project, we will take advantage of unique mouse models to determine whether inhibition of the function of a novel protein can prevent melanoma growth and metastasis to different organs. The results of this study may lead to new therapeutic approaches to control malignant melanoma and other metastatic cancers.
The Mechanism For Combined Immunodeficiency And Autoimmunity Due To STK4-deficiency And Its Broader Application To Human PIDs
Funder
National Health and Medical Research Council
Funding Amount
$648,371.00
Summary
Why do some patients develop autoimmune diseases such as lupus where the immune system makes antibodies that attack its own body? To answer this, we plan to study a disease where a gene responsible for making antibodies is defective. Patients with mutations in the STK4 gene are unable to regulate the selection processes by which only the right cell is chosen to make antibodies. Understanding how STK4 works may help us unlock the mystery of what causes lupus.
Studies On The Role Of The P101 Component Of The Class 1B PI 3-Kinase In Cell Migration And Activation.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
This research will determine the biological role of a protein of unknown function that is likely to participate in movement of white blood cells through the body. The outcome of this research will increase our basic knowledge of how the immune system functions and could lead to alternate therapeutic strategies for the control of autoimmune diseases.
In Vivo Imaging Of Virus-specific T Cell Responses In The Skin
Funder
National Health and Medical Research Council
Funding Amount
$332,258.00
Summary
Effective vaccination against many viral infections such as Herpes Simplex Virus (HSV) may be achieved by directing the cells of the immune system to specific sites in the body where they can lie in wait against the disease. To direct the immune system in this way, we must first understand how immune cells orchestrate themselves in tissues. This project will utilise advanced imaging techniques to study immune cells in real time to understand how they protect against viral infections in the skin.
Cells of the immune system need to recognise characteristic viral and bacterial molecules, in order to identify infection. Some immune cells can detect the presence of viral and bacterial DNA. The cells respond by making a number of anti-viral or anti-bacterial molecules, as well as activating other cells to fight the infection. The effect of bacterial DNA can be mimicked by certain short synthetic pieces of DNA. The potent activity of this synthetic DNA (termed CpG DNA ) is being exploited in a ....Cells of the immune system need to recognise characteristic viral and bacterial molecules, in order to identify infection. Some immune cells can detect the presence of viral and bacterial DNA. The cells respond by making a number of anti-viral or anti-bacterial molecules, as well as activating other cells to fight the infection. The effect of bacterial DNA can be mimicked by certain short synthetic pieces of DNA. The potent activity of this synthetic DNA (termed CpG DNA ) is being exploited in a number of clinical trials for treatment of cancer and allergy, as well as to improve vaccinations. Despite the rapid advance towards clinical application, there is still much basic information to learn about how CpG DNA acts on cells. The molecule to which DNA binds in order to activate the cells is called TLR9. TLR9 is not on the surface of cells, but within cells. In a bacterial infection, cells called macrophages engulf and digest bacteria and release the bacterial DNA within the cell, where it binds to TLR9. In other cases, including when CpG DNA is used therapeutically, the DNA needs to be taken up into the cell. Evidence shows that there is a receptor on the cell surface which binds DNA, and takes it into the cell. In this project we propose to identify this DNA uptake receptor. Apart from the use of CpG DNA, there are a number of other proposals for the therapeutic use of DNA. Although it is known that DNA enters into cells, the route for this has not been established. Whilst CpG DNA can activate immune cells, some other distinct DNA molecules can prevent the activation. We will examine whether these inhibitory DNA molecules bind more effectively to TLR9 than the CpG DNA, but do not activate the cell. These inhibitory molecules are proposed as a therapy for the autoimmune disease lupus, which involves inappropriate responses to DNA, and is thought to involve TLR9. In order to develop therapies, a detailed knowledge of how they work is essential.Read moreRead less
A Novel CCR2-dependent Niche For CD8+ T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$482,549.00
Summary
In this project, we will determine how a protein called CCR2 controls the generation of memory immune responses and whether its activity can be manipulated to enhance vaccination.
I am a cellular immunologist interested in the study of cytokines and other regulatory molecules in inflammatory and immune responses. One key area relates to the effect on sunlight on cell-mediated immunity.