Dissecting Mechanisms Of Generalised Immune Activation And Cellular Dysfunction In HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$422,576.00
Summary
How HIV infection compromises the host immune system is still not well understood. We will study how HIV surface proteins contribute to heightened immune activation during chronic infection. This generalised activation eventually leads to dysfunctional cellular immune responses and loss of partial control of infection. We will additionally investigate the extent and impact of the loss of functional immune responses in chronic HIV infection.
Immune Regulation During Uncomplicated And Severe P. Falciparum And P. Vivax Malaria
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
Malaria is a major global disease that kills over 1 million people every year. Immune responses induced during infection help fight the infection but can also cause tissue damage and thereby worsen disease. This study will determine differences in cellular immune responses during uncomplicated and severe malaria. Better understanding of the role of immune cells in response to infection and disease progression will assist the development of novel treatment interventions and vaccine development.
Understanding The Role Of Chemokine Receptor Modulation In T Cell Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$391,650.00
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. It is therfore important to understand how the movement of these cells through the body is controlled. A better understanding of this process shuld allo ....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. 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 cell activation.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.
T cells play a central role in the immune response. The primary event in T cell activation is the triggering of a specific T cell receptor (TCR). Our studies will examine whether the protein TCPTP antagonises TCR-instigated T cell responses. Our studies may provide important new insights into alternative approaches for manipulating T cell-mediated immune responses in diseased states.
Analysis Of The Molecular Functions Of Perforin: A Critical Role In Tumor Immunosurveillance
Funder
National Health and Medical Research Council
Funding Amount
$318,916.00
Summary
Over the past decade, great steps have been made in defining the key molecules used by killer cells of the immune system that eliminate cancerous- and virus-infected cells and many of these advances have originated in our laboratory. It is now clear that granule-mediated cytolysis is a key mechanism for controlling both primary and metastatic cancers in transplanted syngeneic, allogeneic and xenogeneic tumor models in mice. The pore-forming protein, perforin is indispensable for effective killer ....Over the past decade, great steps have been made in defining the key molecules used by killer cells of the immune system that eliminate cancerous- and virus-infected cells and many of these advances have originated in our laboratory. It is now clear that granule-mediated cytolysis is a key mechanism for controlling both primary and metastatic cancers in transplanted syngeneic, allogeneic and xenogeneic tumor models in mice. The pore-forming protein, perforin is indispensable for effective killer cell function in these models. But the role for perforin expressing killer cells in tumor surveillance against spontaneous tumorigenesis is still hotly debated. Our proposal to study tumor development in perforin-deficient p53-mutant tumor prone mice will enable us to answer this question. Furthermore, the molecular mechanisms by which perforin functions are poorly understood. We therefore also propose to complete a structure-function analysis of perforin using unique tools and information that our laboratory has at its disposal. The long-term goal will be to better understand the function of perforin at the molecular level such that the rationale design of therapeutic perforin inhibitors may become a reality for future regulation of killer cell effector functions in disease.Read moreRead less
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
TSLP And Dysregulation Of Anti-viral Immunity In Atopic Dermatitis
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Eczema (atopic dermatitis) is a frequent allergy in Australia. People with eczema can suffer very severe skin infections with some viruses, including the virus that causes cold sores, but we do not know why this happens. A newly discovered protein called TSLP is now known to be made by skin affected by eczema and there is evidence that TSLP may interfere with the way the body fights viruses. We will examine whether TSLP programs the immune system so that it is less able to fight viruses.