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.
Utilising Human Primary Immunodeficiencies To Study Lymphocyte Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$429,346.00
Summary
Human immunodeficiencies are diseases arising from naturally occurring mutations. In this instance, the specific genes mutated in the immunodeficiencies we study have been identified. However, it is unclear how defects in these genes make an individual manifest as an immune deficient state, rendering them vulnerable to disease. By studying immune cells from these individuals we hope to uncover the normal function of these genes and subsequently provide for new therapies for these conditions.
Signal Integration During The Early B Cell/CD4+ T Cell Interactions In T-dependent Antibody Responses
Funder
National Health and Medical Research Council
Funding Amount
$128,783.00
Summary
Effective humoral immunity results from the complex interaction of B and T lymphocytes. STAT3, CD40L, SAP and ICOS are molecules that are involved in this interaction. Genetic mutations of these molecules result in well defined primary immunodeficiencies underscoring their importance. This study aims to characterise the integration of these early signals as well as other inputs that B cells receive and characterise the CD4+ cells that provide this help.
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.
STAT3-mediated Regulation Of Human Antibody Responses
Funder
National Health and Medical Research Council
Funding Amount
$580,249.00
Summary
The immune system rapidly responds to infectious pathogens to eradicate such microbes and limit the damage they can inflict upon the host. Individuals with primary immunodeficiencies have defects in the development and/or function of the cells of their immune system and are more susceptible to infectious diseases. This study will investigate such individuals to identify functions for specific genes and immune cells in order to understand the requirements for generating effective immune responses ....The immune system rapidly responds to infectious pathogens to eradicate such microbes and limit the damage they can inflict upon the host. Individuals with primary immunodeficiencies have defects in the development and/or function of the cells of their immune system and are more susceptible to infectious diseases. This study will investigate such individuals to identify functions for specific genes and immune cells in order to understand the requirements for generating effective immune responses.Read moreRead less
B Cell Survival And Responsiveness In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
I am an immunologist focused on identifying how B lymphocytes, the cells responsible for producing antibodies, survive and participate in immune responses within the body. I achieve this by using specially designed, genetically modified, mice that allow me to follow B lymphocytes within the body and identify their key genetic and external controls. My work is relevant to vaccine development as well as the control of certain autoimmune diseases and B lymphocyte cancers.
Control Of T Helper Cells In Autoimmunity And Anti-tumour Responses.
Funder
National Health and Medical Research Council
Funding Amount
$434,953.00
Summary
The proposed studies aim to improve our understanding of the factors that regulate a specialised immune cell type called “T helper” cells and their function in models of autoimmune disease and during anti-tumour immune responses. The project will investigate (1) the role of a signalling protein called Interleukin 27 in these processes and (2) how several novel genes, recently found to be associated with the development of MS in humans, influence T helper cell activity.
Follicular T Helper Cells: Critical Regulators Of Humoral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$272,591.00
Summary
B cells are important cells of the immune system that are responsible for producing antibodies in response to infection with pathogens, such as bacteria or viruses, or following vaccinations. In order for B cells to accomplish this task, they require help from a specialised popualtion of T cells, which are another type of immune cell - these are known as follicular T helper (TFH) cells. Under normal circumstances, T cells and B cells specifically interact with one another within lymphoid tissues ....B cells are important cells of the immune system that are responsible for producing antibodies in response to infection with pathogens, such as bacteria or viruses, or following vaccinations. In order for B cells to accomplish this task, they require help from a specialised popualtion of T cells, which are another type of immune cell - these are known as follicular T helper (TFH) cells. Under normal circumstances, T cells and B cells specifically interact with one another within lymphoid tissues such as tonsils, spleens and lymph nodes - here, they engage in a dialogue, the end result of which is the B cells being instructed to produce the appropriate type of antibodies by T cells. However, if tis process is not regulated, the T cells can deliver too little of too much help - this can result in several different types of diseases of the immune system, such as immunodeficiencies (ie insufficient production of antibodies, resulting in individuals becoming susceptible to infections) or autoimmunity (ie production of inappropriate types of antibodies that can recognise cells of the host, resulting in tissue damage and organ failure). The means by which TFH cells instruct B cells to produce antibodies is not completely understood. This project will seek to determine the mechanism whereby TFH cells carry out this important function by performing detailed examination of them follwoing their removal from tissues such as human tonsils and spleens. In doing so, we hope to design approaches that will allow the function of TFH cells to be improved in cases of immunodeficiencies, or suppressed in situations of autoimmune diseases.Read moreRead less
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.