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
Understanding And Improving The Non-human Primate Model For Human Immunodeficiency Virus Vaccine-induced Mucosal Immunity.
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
The overall aim of this project if to generate a more effective vaccination for HIV, using an animal model of the disease. We will test vaccination methods targeting immunity to the reproductive tract, in order to attack the virus where it is usually first encountered.
Regulation Of T-cell Activation In The Airway Mucosa Of Rats Expressing Low Versus High IgE Responder Phenotype
Funder
National Health and Medical Research Council
Funding Amount
$713,058.00
Summary
We have established an experimental rat model of allergic airways inflammation which mimics human asthma. Interactions occurring between airway mucosal dendritic cells and CD4+ Th2 (effector) cell populations are responsible for the late phase response (LPR) component of asthma exacerbations, including airways hyperresponsiveness (AHR). We have previously demonstrated that termination of the LPR and prevention of its continual recurrence in the face of ongoing aeroallergen challenge is establish ....We have established an experimental rat model of allergic airways inflammation which mimics human asthma. Interactions occurring between airway mucosal dendritic cells and CD4+ Th2 (effector) cell populations are responsible for the late phase response (LPR) component of asthma exacerbations, including airways hyperresponsiveness (AHR). We have previously demonstrated that termination of the LPR and prevention of its continual recurrence in the face of ongoing aeroallergen challenge is established via the induction of a state of dynamic equilibrium, mediated by local T regulatory cells (Treg) which act to functionally silence local Th2 memory (effector) cells. Maintenance of protective Treg activity is dependent upon continuing allergen exposure as cessation of exposure leads to waning of Treg numbers and function and release of mucosal allergen specific Th2 cells from control. These studies have primarily involved low IgE responder (LR) PVG rats (normals or nonatopics). The present study will focus on elucidating the control of Th2 dependent immune responses to inhaled antigen in high IgE responder (HR) BN rats (atopics). Studying these two strains in parallel enables a comparison between the extremes of the spectrum of susceptibility to both the induction and the expression of Th2 immunity in the airways. A more detailed understanding of the cellular interactions occurring within the airway mucosa and draining lymph nodes and the mechanisms responsible for the maintenance of immunological homeostasis within the airways will provide new insights into the pathogenesis of inflammatory airway diseases such as atopic asthma. This will enable further development and possibly illuminate other avenues of intervention for more effective therapeutic strategies used in the control of asthma, which is the long term goal of this research.Read moreRead less
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.
The Role Of IL21 In Integrating Proliferation, Migration And Differentiation Following B Cell Activation.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Immunity is essential to health and requires the production of antibodies. The best antibodies are made by B-cells coming from specialised structures, called germinal centres (GC). To understand why sometimes immunity is excellent - childhood vaccines - and other times not - HIV infection, aged people - we need to understand what happens inside GC. Our prediction is that by understanding GC B cell behaviour, we will resolve good from poor immune responses and thereby develop improvements.
Determining The Structure Of A Soluble Cytokine Receptor Complex
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
There is a pressing need to develop improved therapeutics to treat many forms of cancer and respiratory diseases. This proposal concerns the biochemical investigation of a group of protein hormones and their associated receptors that are implicated in blood cell cancers and for which current treatments are only partly effective . Our work will focus on determining the 3-dimensional shape and function of this group of proteins in complex with one another which will provide us with an understandin ....There is a pressing need to develop improved therapeutics to treat many forms of cancer and respiratory diseases. This proposal concerns the biochemical investigation of a group of protein hormones and their associated receptors that are implicated in blood cell cancers and for which current treatments are only partly effective . Our work will focus on determining the 3-dimensional shape and function of this group of proteins in complex with one another which will provide us with an understanding of how these proteins communicate with one another. This information may provide a basis for the design of new drugs that can specifically block the activity of these protein hormones, thereby providing new treatment possibilities for these blood cell cancers.Read moreRead less
Investigating Type I Interferon-mediated Immune-suppression During Plasmodium Infection
Funder
National Health and Medical Research Council
Funding Amount
$561,617.00
Summary
Some infections tend to afflict us only once in our lifetimes, for example chickenpox. This is because our bodies develop immunity to these infections relatively easily. The same is not true for malaria. It is thought that our immune systems are somehow suppressed during this disease. This project aims to understand how the immune system is suppressed during malaria infection, in order that we can block this process, and help our bodies fight this disease more effectively.
Memory CD4 T Cells That Harbour The Reservoir Of Latent HIV Infection: Their Antigen Specificity, Function And Frequency Of Antigen-drivien Reactivation
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Current antiretroviral therapy for HIV-1 infection is able to suppress viral replication, but cannot eradicate it completely. Upon cessation of antiviral therapy, viral recrudescence is prompt, and most likely arises from latent reservoirs of HIV in various cellular compartments. The aim of this research is to characterise which subsets of CD4 T cells that are the target of HIV infection harbour HIV infection, including describing their function and individual target antigen specificities.