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.
Mechanisms Of B Cell Immunodominance To Influenza Virus
Funder
National Health and Medical Research Council
Funding Amount
$617,611.00
Summary
Current influenza vaccines elicit poor protection against viruses undergoing rapid change or emerging from animal reservoirs. We will define the basis for why highly conserved sites of virus vulnerability, such as the hemagglutinin "stem" domain, are poorly targeted by current vaccines and will assess novel hemagglutinin stem-based vaccines in macaque models of human influenza. Our results will guide the rational design of next-generation vaccines for influenza.
Identification Of Novel HCV-specific B Cell Epitopes Which Induce Broad Neutralising Antibodies
Funder
National Health and Medical Research Council
Funding Amount
$482,480.00
Summary
This research project will study humans who have been exposed to multiple Hepatitis C virus infections. We will be examining their immune response with the aim to identify subjects with antibodies that are able to neutralise a diverse range of hepatitis C virus variants. These antibodies will be used to identify novel targets for a vaccine directed against Hepatitis C virus.
Extending Life After Lung Transplantation – Defining The Structural And Immunological Drivers Of Chronic Lung Allograft Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$739,190.00
Summary
Lung Transplantation (LTx) saves life. However, chronic rejection limits survival after LTx compared to other solid organ transplants. Chronic rejection develops when the LTx recipient produces antibodies against the donor lung. With a team of global leaders in the field we will dissect the antibody response to LTx. By better understanding the immune drivers of antibody-mediated rejection, we aim to reduce the incidence of chronic rejection thereby improving survival after LTx.
Multiple Paths Of TFH Differentiation And Their Impact On B Cell Protection Against Infection
Funder
National Health and Medical Research Council
Funding Amount
$923,466.00
Summary
Collaboration between T and B cells is crucial for immune protection and underpins current vaccine strategies. We have revealed an unappreciated flexibility that exists in T cell responses which varies the instructions they give B cells. It is likely this tailors immune responses to ensure protection to countless infectious diseases. This project uses cutting-edge technologies to understand this flexibility and has important implications for vaccine design and treatment of infectious disease.
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.
Determining The Essential Regulators Of Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$768,612.00
Summary
Plasma cells produce the antibodies that are essential to protect us from pathogenic microorganisms and provide the basis for the beneficial effects of vaccination. Plasma cells can also cause disease through the production of antibodies against our own body, for example in Lupus and in the blood cell cancer multiple myeloma . Our research aims to understand the genetic regulation of antibody production, with an aim to "switch off" inappropriate antibody supply in disease.
Determining The Role Of DOCK8 In CD4+ T And B Cell Differentiation And Its Implications On Autosomal Recessive Hyper IgE Syndrome (AR-HIES)
Funder
National Health and Medical Research Council
Funding Amount
$512,600.00
Summary
Autosomal recessive hyper IgE (AR-HIES) syndrome due to mutations in DOCK8 is a rare primary immunodeficiency whereby patients present with susceptibility to severe and recurrent viral infections as well as an increased risk of developing cancer, severe food and environmental allergies, and atopic disease characterised by hyper IgE and extreme eosinophilia. This grant will investigate how abnormal DOCK8 function in CD4+ T cells and B cells contributes to disease pathogenesis in AR-HIES patients.