This project proposes to identify novel components and develop new inhibitors of an epigenetic pathway known to control the immune cells that cause allergic asthma. Our objective is to use these drugs to treat allergic disease.
Natural Treg are dependent on the transcription factor FOXP3, but the mechanism of action of FOXP3 is only now becoming defined for human Treg. Tregs are critical for a balanced, responsive immune system, and deviation from this balance results in autoimmune diseases or persistence of cancers. In order to intervene to treat these disease it is essential to first know what makes a normal Treg function, and to then compare this with the disease so that faulty genes can be targeted for intervention ....Natural Treg are dependent on the transcription factor FOXP3, but the mechanism of action of FOXP3 is only now becoming defined for human Treg. Tregs are critical for a balanced, responsive immune system, and deviation from this balance results in autoimmune diseases or persistence of cancers. In order to intervene to treat these disease it is essential to first know what makes a normal Treg function, and to then compare this with the disease so that faulty genes can be targeted for intervention with new drugs or a cell therapy.Read moreRead less
Most individuals infected with hepatitis C virus (HCV) develop progressive liver disease. A vaccine is urgently needed, and needs to mimic the immune responses seen in the minority of individuals who clear infection. However, there are large gaps in our understanding of these responses as most acute infections cause no illness and pass unnoticed. This project will fill these gaps by detailed immunological and virological analysis of a large group of subjects with early infection.
Adoptive Cell Transfer Incorporating Vaccination (ACTIV) Therapy For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
We have made a breakthrough in a new treatment for cancer that can destroy large tumours in mice. The treatment involves a transfusion of white blood cells and an injection of a vaccine. In this project, we will seek to understand how the treatment works, and apply it to human white blood cells in preparation for a clinical trial in cancer patients.
The Opposing Genetic Networks Underlying Plasticity Of Humoral Responses
Funder
National Health and Medical Research Council
Funding Amount
$667,783.00
Summary
The immune system makes antibody to clear bacterial and viral pathogens. Specialised types of antibody are needed for different pathogens. This project will study genetic changes that determine the specificity of an antibody response. Regulation of these genes may prohibit production of antibodies and inflammatory mediators that attack the body rather than foreign pathogens. Understanding these processes will identify points of therapeutic intervention for patients with immune disorders.
Generating Stronger And Smarter T Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$310,332.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. These cells can then be given back to the patient, which can sometimes cause cancer regression. However, often the white blood cells lack strength, or they lack the ability to distinguish between tumour and normal tissues of the body. In this project we seek to make stronger and smarter white blood cells that can deliver a lethal hit against tumours without damaging essential organs of the body.
The Role Of The Transcription Factor Blimp-1 In Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$642,674.00
Summary
Regulatory T (Treg) cells function by suppressing immune system activity, ensuring that our immune system does not mount a response against our own tissue. In cancer, Treg cells suppress anti-tumour immunity, facilitating tumour growth. Recently we have identified a group of active Treg cells that may be the key drivers of immune response regulation. Our work will examine the role of these active Treg cells in tumour immunity, opening the door to more effective targeting of Treg cells in cancer.
Delineating Aberrant Adaptive Immune Responses Due To Germline Mutations In The PI3K Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$975,476.00
Summary
Activation of immune cells is required to generate appropriate immune responses that protect is from disease caused by pathogens. The inability to receive the correct type of signals causes immunodeficiency. The PI3 kinase pathway is central to immune cell activation – and genetic errors in this pathwat compromise the functioning of immune cells. We will investigate the nature of these defects and pursue avenues of overcoming them using pharmacological inhibitors of the PI3K pathway.
Leptin As A Natural Regulator Of TFH Cell Differentiation And Vaccination Response
Funder
National Health and Medical Research Council
Funding Amount
$594,901.00
Summary
Follicular helper T (Tfh) cells constitute a CD4+ T cell subset that plays an instrumental role to support protective antibody responses in infection and vaccination. Although malnutrition is associated with poor vaccine responses and increased risks of infections, the mechanism is poorly understood. We will investigate the mechanism by which leptin, a hormone secreted by adipose cells, regulates Tfh cell function and vaccination response.
Sytemic And Mucosal Functional Antibodies In Protection Against HIV
Funder
National Health and Medical Research Council
Funding Amount
$559,501.00
Summary
Only one human HIV vaccine has shown any level of protective efficacy. However the mechanisms behind how this vaccine was protective are still not fully understood. Additionally, HIV is primarily transmitted through mucosal sites, however very little is know about vaccine immune responses at these sites. Thus this proposal aims to further define the mechanisms of antibody protection against HIV at both systemic and mucosal locations, in order to guide future HIV vaccine design efforts.