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.
Determining The Role Of Rel/NF-kB Transcription Factors In CD8 T Cell Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur f ....NF-kB proteins comprise a family of transcription factors that regulate key genes involved in immune responses, inflammation, cell death and proliferation. This family of proteins are potential drug targets for treatment of various diseases. How and when such inhibitors are used in clinical situations depends on understanding how and which cells of the immune system are specifically affected by the absence of NF-kB proteins. In a number of treatment settings intercurrent viral infections occur frequently and therefore there is an even greater need to understand how the immune system may be affected or compromised in response to the primary treatment. This work will provide insights into the cellular and molecular mechanisms affected by the absnece of a particular NF-kB family member (NF-kB1) in CD8 T cells during normal T cell homeostasis and when challenged with viruses. What we learn from our experiments could have important implications for the development of vaccines.Read moreRead less
Elucidating Immune Responses By Single Cell Pedigree And Tracing Analysis
Funder
National Health and Medical Research Council
Funding Amount
$666,950.00
Summary
To develop vaccines and to combat autoimmunity, we need to understand how initial immune activation influences the fate of immune cells and their progeny. To achieve this, we have developed microscopic techniques and analytical software with which to observe how initial signalling processes in the parent immune cell influence the death, proliferation and differentiation of its daughters, granddaughters and further progeny. We will use these approaches to determine how immune cell fate is control
Dendritic Cell-mediated Induction Of T Cell Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$654,725.00
Summary
Australia has some of the highest rates of immune-mediated diseases in the world. These diseases include autoimmune, allergic and inflammatory conditions. We will use a mouse model to study how dendritic cells can prevent the onset of these conditions by inactivating the immune cells that cause them. Our findings will aid in understanding why these diseases develop and how they may be prevented and treated.
The initial step of T cell activation of how the external ligand binding is translated to an increase of receptor phosphorylation at the cytoplasmic side is remain poorly understood. It is believed that the loss of immune recognition in cancer and over reactivity in auto-immune diseases are caused by abnormality of this transmembrane signalling transduction. Clarification of this molecular machinery can provide a molecular basis of those diseases and guidelines of more effective therapies.
Controlling Life And Death Of Dendritic Cell Subsets For Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$639,577.00
Summary
Dendritic cells are pivotal in orchestrating immune responses; for example, they can turn immune cells into assassins to kill virus infections. Their function is so diverse that different dendritic cells do different jobs. There are many genes that control life and death of cells but those that are important for each specialised dendritic cell have not been comprehensively studied. Drugs that affect the proteins made by such genes selectively may be a new way of controlling immune responses.
The Cell Death Mechanisms That Control Regulatory T Cell Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$583,782.00
Summary
A central question in immunology is how to prevent destructive immune responses (e.g. autoimmune disease) and initiate productive immune responses (e.g. against cancer). A major breakthrough in this area was the discovery of special immune cells, called a Regulatory T Cells. We propose to discover the genes that determine whether these cells live and die. We will use this information to control appropriate numbers and function of Regulatory T Cells to modify the immune system.
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.
Characterising And Visualising Cross-presenting Dendritic Cells Following Cutaneous Vaccinia Infection
Funder
National Health and Medical Research Council
Funding Amount
$415,682.00
Summary
Live imaging of cells within lymphoid organs provides a valuable tool allowing insight into how immune responses are initiated. Utilising novel reagents we will visualise and define these events following cutaneous infection with vaccinia virus.