Investigating B Cell Development, Maintenance And High-affinity Antibody Production By ENU Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
B cells are essential for the protection against infections. This application aims to identify new genes that are crucial for the development or function of B cells and will investigate how mutations in newly discovered genes contribute to defects in the development and function of B cells and the pathogenesis of B cell leukaemia.
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.
Control Of Pathogenic Antibody Responses In Humans
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Deficient or inappropriate antibody responses are at the core of many autoimmune diseases, allergies, food intolerances, and often explain the failure of vaccination strategies. Specialised follicular T cells control the quality of antibodies produced by B cells. This fellowship will combine basic studies investigating B cell helper or regulatory follicular T cells in humans with genetic studies identifying the causes of autoantibody-driven diseases. The results will uncover targeted therapies.
Characterisation Of An Antigen Presenting Cell Unique To Spleen
Funder
National Health and Medical Research Council
Funding Amount
$420,606.00
Summary
The body depends on a range of defence mechanisms to remove invaders that enter by various routes. Antigen presenting cells are central to immunity in that they engulf and destroy dead cells and pathogens and present pieces of those pathogens or 'antigens' to white blood cells called T and B lymphocytes. These cells then start to fight the infection or disease. A new type of antigen presenting cell will be investigated for its particular ability to arrest blood-borne pathogens and disease.
I am an immunologist focusing on understanding how can we combat chronic infections while preventing autoimmunity. This proposal aims to investigate how a poorly understood subset of lymphocytes called Tfh cells are regulated to promote the formation of protective antibodies, and prevent development of harmful antibodies that go on to cause or exacerbate diseases such as lupus, rheumatoid arthritis and type 1 diabetes. Our discoveries will illuminate novel drug targets for these diseases and hel ....I am an immunologist focusing on understanding how can we combat chronic infections while preventing autoimmunity. This proposal aims to investigate how a poorly understood subset of lymphocytes called Tfh cells are regulated to promote the formation of protective antibodies, and prevent development of harmful antibodies that go on to cause or exacerbate diseases such as lupus, rheumatoid arthritis and type 1 diabetes. Our discoveries will illuminate novel drug targets for these diseases and help generate more potent vaccines.Read moreRead less
Modeling Human Actin Related Protein 2/3 Complex Subunit 1B (ARPC1B) Deficiency In Mice
Funder
National Health and Medical Research Council
Funding Amount
$755,005.00
Summary
The actin cytoskeleton forms the structure that not only keeps cells in their normal shape but is also essential for the movement of cells and for interaction between cells. We have recently identified the first patients with an immunodeficiency caused by a defect in a gene called ARPC1B, which plays a crucial role in the regulation of actin. Through the investigation of novel mouse models we will elucidate the pathomechanism underlying the disease of these patients.
Specialised Subsets Of T Follicular Helper Cells In The Control Of Infection And Immune Pathology
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Defective or uncontrolled production of antibodies leads to increased susceptibility to infection, allergies, and autoimmune diseases. A type of T cell called follicular helper (Tfh) has emerged as a key controller of both protective and pathologic antibody production. We have data suggesting there are specialised Tfh subsets, each controlling different stages and outcomes of antibody responses. Identifying how each subset is regulated and functions will provide novel targets to treat these chro ....Defective or uncontrolled production of antibodies leads to increased susceptibility to infection, allergies, and autoimmune diseases. A type of T cell called follicular helper (Tfh) has emerged as a key controller of both protective and pathologic antibody production. We have data suggesting there are specialised Tfh subsets, each controlling different stages and outcomes of antibody responses. Identifying how each subset is regulated and functions will provide novel targets to treat these chronic debilitating diseases.Read moreRead less
Antigen Receptor Sharing By Lymphocytes During An Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$286,328.00
Summary
A successful immune response relies on the ability of immune cells to quickly mount a specific offensive against invading foreign pathogens like bacteria or viruses. The specificity of this offensive is governed by receptors that can recognise pathogens. To survive an infection the immune system must rapidly expand the number of immune cells that have receptors that recognise, and can therefore specifically combat, the infection. The underlying theory of immunology, the clonal selection theory, ....A successful immune response relies on the ability of immune cells to quickly mount a specific offensive against invading foreign pathogens like bacteria or viruses. The specificity of this offensive is governed by receptors that can recognise pathogens. To survive an infection the immune system must rapidly expand the number of immune cells that have receptors that recognise, and can therefore specifically combat, the infection. The underlying theory of immunology, the clonal selection theory, states that this expansion is mediated by the proliferation of immune cells selected on the basis of expressing a pathogen specific receptor. We hypothesise that in addition to this proliferation the immune system may also expand the number of immune cells expressing pathogen-specific receptors by transferring these receptors between cells by a means of cell-membrane sharing. Indeed, we have evidence that this does occur both in the test tube and in animals and can function to amplify the number of immune cells that can specifically recognise a pathogen and thereby help with immune response development. This grant aims to further advance our understanding of this novel phenomenon.Read moreRead less
Regulation Of T Follicular Helper Cell Development And Effector Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$419,197.00
Summary
Immune cells mature into distinct populations with specialized functions. One subsets are T follicular helper (TFH) cells which are important for instructing B cells to produce antibodies following infection or vaccination. The means by which TFH cells are generated are unknown. We will determine mechanisms whereby TFH cells are produced and how they function. We hope to design approaches that will modulate the function of TFH cells in cases of immunodeficiencies, autoimmunity or vaccination.