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Investigating The Role Of TCR Avidity In Influenza Virus-specific CD8 T Cell Responses
Funder
National Health and Medical Research Council
Funding Amount
$83,142.00
Summary
One of the constituents of the immune system is the cytotoxic, or killer, T cells and these are important in the overall protection from viral infection. Activation of these T cells is mediated by signalling through the T cell receptor (TCR). This study will definitively determine how the strength with which the TCR binds to the activating ligand, can influence the quality of virus-specific T cell immune responses after infection. This has implications for vaccine design.
Immune Correlates Of Protection Against HCV - A Potential Role For NK Cells And NKR Expression On T Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$72,754.00
Summary
Hepatitis C virus (HCV) poses a major public health problem with ~200 million people infected worldwide and no available vaccine. Injecting drug users (IDUs) are the major risk group, with 75% of infected individuals progress to chronic infection, which can then lead to liver cirrhosis and hepatocellular carcinoma. However, about 20% of a given cohort of IDUs remains uninfected. This project is therefore focused on understanding the innate immune mechanisms behind this protection.
Defining The Role Of Lymphotoxin Alpha In Experimental Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$158,250.00
Summary
Malaria kills millions of children every year. A major cause of death is cerebral malaria (CM) resulting from Plasmodium falciparum infection. At present, there is no effective vaccine available and drug-resistant parasites are widespread. CM is a serious neurological condition characterised by the sequestration of infected red blood cells (iRBC) in cerebral blood vessels. This event is thought to initiate a cascade of inflammatory reactions that ultimately lead to cerebral damage and often deat ....Malaria kills millions of children every year. A major cause of death is cerebral malaria (CM) resulting from Plasmodium falciparum infection. At present, there is no effective vaccine available and drug-resistant parasites are widespread. CM is a serious neurological condition characterised by the sequestration of infected red blood cells (iRBC) in cerebral blood vessels. This event is thought to initiate a cascade of inflammatory reactions that ultimately lead to cerebral damage and often death. The factors that cause the sequestration of iRBC in the brain are poorly understood. In this project, we will use an experimental model to define the changes that occur in the cerebral vessels during malaria. The identity of the cells and molecules that mediate the binding of iRBC to the blood vessels of the brain will be identified. It is anticipated that results from this work will increase our understanding of the development of pathology in the brain, as well as identify potential targets for modulation to prevent disease.Read moreRead less
Modulation Of HIV-1 Specific T Cell Function By Toll-like Receptor Ligands
Funder
National Health and Medical Research Council
Funding Amount
$214,584.00
Summary
Toll-like receptors (TLR) are highly conserved molecules which allow cells to recognize foreign materials. Factors that bind to these TLRs are called ligands. Ligands that activate or suppress TLR may play a crucial role in influencing how the immune system recognizes and controls HIV. A better understanding of the mechanisms by which TLR ligands, including components of HIV-1, modulate T cell function will open up new avenues for the design of immunotherapeutic interventions and vaccines.
Investigations Into The Architectural And Biophysical Features Of Optimal T Cell Receptor Design
Funder
National Health and Medical Research Council
Funding Amount
$251,877.00
Summary
Humans evolve slowly, pathogens and cancer evolve quickly. Unsurprisingly, our immune systems often lose this arms race and we irreversibly succumb to disease. Catastrophically, >26 million people are lost every year to the these causes. This project will use a new technology to rapidly advance the evolution of human immune receptors to construct a class of super-receptor. These super-receptors may prove decisive weapons in the fight against cancer and infectious disease.
Interplay Of Innate And Adaptive Immunity To Influenza A Virus
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
Influenza is an acute febrile respiratory illness caused by influenza virus infection, and may trigger potentially life-threatening complications especially in the young and elderly. Immunity against influenza virus involves integration of the innate and adaptive immune system. We will use cutting-edge 2-photon microscopy to determine the orchestration of innate and adaptive immune cell interactions during viral infection. Results may provide for enhanced therapeutic or protective measures.
Discovery Of Long CD8+ T Cell Epitopes Uncovers A Hidden Reservoir Of Immunodominant, Anti-tumour Responses
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
Stimulating killer T cells to eliminate tumours has been one of the ultimate yet elusive goals of cancer vaccine development. Vaccines aimed at stimulating killer T cells are similar to those generated under natural conditions. However, special strategies are needed to vaccinate beneficial killer T cells that are not normally part of the natural immunity. In this project, we will explore such a scenario and dissect the related mechanisms contributing to such differential immune outcomes.
The Role Of Epigenetic And Transcriptional Regulation In CD8+ T Cell Effector Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$72,571.00
Summary
All cells contain DNA that is tightly wrapped around proteins, whereby changes in the structure allow for the expression of proteins. Cells of the immune system express proteins that can resolve viral infections. This study plans to examine the factors mediating the changes in DNA that allow for the expression of these proteins in immune cells. Insights will enable a greater understanding of how these proteins are generated and maintained, and hence will have implications for vaccine design.
Chemokine And Chemokine Receptor Regulation Of T Lymphocyte Traffic To Lymph Nodes
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
The movement of white blood cells from the bloodstream into the tissues is a key component of how we defend ourselves against infection and cancer, and also develop unwanted illnesses such as allergy. In particular, the migration of cells into lymph nodes is a critical step in the development of an efficient immune response. Surprisongly little is known about the control of this important cell trafficking process. In this research, the signals that control the movement of white blood cells are b ....The movement of white blood cells from the bloodstream into the tissues is a key component of how we defend ourselves against infection and cancer, and also develop unwanted illnesses such as allergy. In particular, the migration of cells into lymph nodes is a critical step in the development of an efficient immune response. Surprisongly little is known about the control of this important cell trafficking process. In this research, the signals that control the movement of white blood cells are being studied, notably a specialised family of immunological hormones, known as chemokines. Our initial studies suggest that chemokines are indeed the factors which control the traffic of the most important cell type - T cells, into lymph nodes. This research will examine how the activity of specific chemokines controls the influx of particular groups of T cells and subsequently determines the characteristics of the overall immune response taking place in the lymph node.Read moreRead less