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Epigenetic Regulation Of CD8+ T Cell Function And Memory.
Funder
National Health and Medical Research Council
Funding Amount
$578,171.00
Summary
Upon virus infection, a subset of white blood cells, called killer T cells, are recruited to fight the infection. This proposal aims to examine molecular changes that occur within killer T cells and impart their specific function. We also aim to understand how killer T cells are _programmed� as they establish immunological memory. This proposal will provide insights important for the design and improvement of vaccine strategies to fight pathogens such as influenza, HIV and even tumors.
Physiologic And Aberrant DNA Recombination In B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
B cells produce antibody which is critical to fight infection. In order to perform this function, antibody genes must first be modified by immune enzymes. However, abnormal DNA attack by these enzymes outside of antibody genes can result in B cell cancer. How the immune system detects and destroys cancerous B cells is poorly understood. This research will provide insight into these processes, and in doing so will further our understanding of how B cell cancers develop and how they are destroyed.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
We know that many parts of viruses are displayed to the immune system, but infection can also result in the display of fragments of our body's own proteins (self-peptides). We will apply cutting-edge technology to find all the virus- and self-peptides that are recognised by the immune system during infection with a vaccine virus and influenza virus. This will help us understand how the body fights infection and perhaps why infection can sometimes start autoimmune diseases.
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.
The immune system is the essential complex barrier that protects the organism for infections and some malignancies. Despite considerable efforts, the mechanism by which immune cells kill dangerous unwanted cells is poorly understood. This project will investigate the mechanism of action and the role in human pathologies of a key component of the immune system, a toxic protein perforin.
We will work with Coridon Pty Ltd to optimize the practical administration of a vaccine designed to cure people already infected with cancer-promoting papilloma viruses.
Determining The Biological Significance Of Allelic Sequence Variation Within The T Cell Receptor Loci
Funder
National Health and Medical Research Council
Funding Amount
$627,549.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific T cell receptors (TCRs). This project will investigate the importance of genetic variation in the TCR genes in influencing how we fight infections. Advances in these areas will assist in understanding susceptibility to some autoimmune diseases as well as aiding in the development of new "intelligent" vaccines and individualised therapeutics.
The Role Of Long Peptide Epitopes In Antiviral CD8+ T Cell Recognition.
Funder
National Health and Medical Research Council
Funding Amount
$434,652.00
Summary
The immune response to viral infection involves killer T cell recognition of small viral peptides presented by infected cells. Researchers have been attempting to identify the viral peptides that are recognised by T cells. Although these studies have been successful, the major aim of this project is to investigate if the role of unusually long peptides has been underestimated. This project should lead to enhanced monitoring of immune responses and improvements in vaccine design.
Follicular Cytotoxic T Cell Differentiation And Function In Infection And B-cell Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$963,892.00
Summary
Cytotoxic T cells eliminate infected or cancerous cells, constituting a major arm of the immune defence. In this study, we will investigate a subset of cytotoxic T cells that particularly migrate into B cell follicles to control infection and malignancy. Understanding of the differentiation and function of this subset, termed as follicular cytotoxic T (TFC) cells, will help us to develop new strategies to treat EBV and HIV infections as well as B cell lymphomas.