Mechanisms Of Mcl-1- And Bcl-2-mediated Resistance To Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$439,796.00
Summary
Anti-cancer therapies that target either the mitochondrial or death receptor pathways of apoptotic cell death are being developed and in clinical trials. In certain cancer cells, the tBid protein links the two pathways, making the death receptor pathway dependent on the mitochondrial pathway. Our studies will test how tBid links the two pathways and how the link might be bypassed, potentially indicating means of improving the effectiveness of treating cancer by targeting death receptors (e.g. TR ....Anti-cancer therapies that target either the mitochondrial or death receptor pathways of apoptotic cell death are being developed and in clinical trials. In certain cancer cells, the tBid protein links the two pathways, making the death receptor pathway dependent on the mitochondrial pathway. Our studies will test how tBid links the two pathways and how the link might be bypassed, potentially indicating means of improving the effectiveness of treating cancer by targeting death receptors (e.g. TRAIL).Read moreRead less
Dissecting Apoptosis And IL-15 Dependent Homeostasis Pathways Of Natural Killer (NK) Cells
Funder
National Health and Medical Research Council
Funding Amount
$423,809.00
Summary
We will investigate how the cytokine IL-15 regulates the homeostasis of natural killer (NK) cells. NK cells are critical for immune responses against invading viruses or bacteria or upon detection of transformed cells. NK cells are primed to attack infected or transformed cells and are rapidly activated by direct interaction or by soluble signals. Knowledge of how NK cells development and how their numbers and function are controlled is paramount to understanding infectious disease immunology an ....We will investigate how the cytokine IL-15 regulates the homeostasis of natural killer (NK) cells. NK cells are critical for immune responses against invading viruses or bacteria or upon detection of transformed cells. NK cells are primed to attack infected or transformed cells and are rapidly activated by direct interaction or by soluble signals. Knowledge of how NK cells development and how their numbers and function are controlled is paramount to understanding infectious disease immunology and developing better immuno-therapies.Read moreRead less
Serological Responses To Anal HPV Infection: Characterising The Natural History Of Anal HPV
Funder
National Health and Medical Research Council
Funding Amount
$220,506.00
Summary
Human papillomavirus (HPV) causes 90% of anal cancer. Anal cancer rates are 20-100 times higher in gay men than other men. The natural history of anal HPV infection and progression to cancer is not completely understood. This study measuring antibodies to HPV will be part of the ongoing Study of the Prevention of Anal Cancer. We aim to show 1) if infection provides any immunity, which will inform HPV vaccination of older gay men and 2) whether antibodies could be used as a marker of cancer risk.
Cytotoxic T Lymphocyte Synapse Formation And Serial Killing: When Breaking Up Is Hard To Do.
Funder
National Health and Medical Research Council
Funding Amount
$626,688.00
Summary
Killer T cells are a specialised group of immune cells, which destroy cancerous and infected cells. When killer T cells find a target, they attach and secrete toxic molecules. It then detaches from the dying target, so that it may go on to kill other cells. If it doesn’t detach properly, it remains bound to the target cell and results in an improper immune response. This proposal will investigate how the killer cell detaches, which is essential for an efficient immune response.
Mechanisms By Which Varicella Zoster Virus And Herpes Simplex Virus Control Host Functions To Enhance Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$631,999.00
Summary
Varicella Zoster Virus and Herpes Simplex Virus are alpha-herpesviruses that cause diseases in a majority of the human population. This proposal will explore issues fundamental to disease and pathogenesis of these two closely related herpesviruses, focusing on how these viruses can control host function. In particular, we will define the interactions between these viruses and the natural killer (NK) cell response.
Dissecting Immune Responses To Salmonella Infection
Funder
National Health and Medical Research Council
Funding Amount
$415,797.00
Summary
Successful treatment of Salmonella infections requires a detailed understanding how Salmonella growth is controlled. This project will examine the role of white blood cells, will reveal how they contribute to the control of Salmonella infections and will test novel treatment options. The outcome of this project will significantly advance our understanding of immune responses against Salmonella.
Structural And Functional Investigation Of Killer-Cell Immunoglobulin-like Receptors
Funder
National Health and Medical Research Council
Funding Amount
$546,966.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used as a guide in the selection of bone marrow donors in the treatment of leukaemias as well as understanding how we fight infections.
Development, Regulation And Role Of Innate Immunological Memory In Malaria
Funder
National Health and Medical Research Council
Funding Amount
$563,860.00
Summary
Innate immunity is traditionally considered to be a short-lived, non-specific first line of defense against pathogens. However, recent reports suggest that innate immune cells can learn from previous pathogen encounters, resulting in enhanced responses on repeat infections with the same pathogen. We will study the role and regulation of innate immunological memory during malaria infection. This will advance our understanding of malaria immunology and will likely aid in the development of vaccine ....Innate immunity is traditionally considered to be a short-lived, non-specific first line of defense against pathogens. However, recent reports suggest that innate immune cells can learn from previous pathogen encounters, resulting in enhanced responses on repeat infections with the same pathogen. We will study the role and regulation of innate immunological memory during malaria infection. This will advance our understanding of malaria immunology and will likely aid in the development of vaccines.Read moreRead less
Identification Of E-protein Complexes Controlling Natural Killer Cell Fate And Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$683,742.00
Summary
Diverse immune cell types are essential for effective broad-spectrum immunity. Master regulators control this diversity and have a well-characterized role in the development of antigen-specific immunity. In contrast, we lack mechanistic understanding of how master regulators control antigen-unspecific, innate immunity. Understanding the mechanism behind this will explain how diverse white blood cells can develop and reveal strategies to skew their development to improve immunity in humans.
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.