Role Of SPPL2A On B Cell Survival And Antibody Production In Mice And Humans
Funder
National Health and Medical Research Council
Funding Amount
$592,989.00
Summary
B lymphocytes are a specialised type of blood cells that produce antibodies in response to a pathogen or a vaccine. We have recently discovered that all mature B cells depend for their survival on a previously unknown protein called SPPL2A. This application will investigate the molecular mechanism through which SPPL2A contributes to the survival of B cells. We will also investigate if humans with currently unexplained B cell deficiency have mutations in SPPL2A.
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.
Genotypes And Phenotypes Of Human Primary Non-congenital Antibody Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$544,692.00
Summary
Antibodies represent a key component of the immune system, and a particularly important in defence against bacterial and viral infections. In some individuals, antibody production fails, rendering them more susceptible to infection. In most cases, the mechanism of antibody failure is unknown. This project seeks to determine the genetic and cellular mechanisms of antibody failure. This could improve diagnosis for immune deficiency, and improve our overall understanding of the immune system.
Understanding The Role Of The Putative Phospholipid Translocase ATP11c In B Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$455,153.00
Summary
The immune system protects humans against recurrent infections with a wide range of pathogens. Formation of antibodies is a crucial element of the immune response. Defects in the production of antibodies can lead to recurrent and often life-threatening infections. This project seeks to understand a genetic defect in mice resulting in an almost complete absence of antibody producing cells, thereby causing a disease that is similar to some forms of human immunodeficiency.
How BANK1 Pathway Defects In B Cells Cause Human Lupus
Funder
National Health and Medical Research Council
Funding Amount
$1,316,839.00
Summary
Autoimmune diseases affect 1 in 20 Australians and are incurable. To find effective therapies, we need to understand the genes that cause disease in humans. We have sequenced the entire genome of patients with an autoimmune disease and found several patients carrry two mutations in genes important for activation of B cells and shown these mutations cause disease. We plan to understand how these genes prevent autoimmunity, and to identify the best treatment for patients with these mutations.
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.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
Uncovering The Basis Of Inflammatory And Immunodeficiency Diseases
Funder
National Health and Medical Research Council
Funding Amount
$15,718,075.00
Summary
A world-class team from 3 institutions, spanning disciplines of clinical and experimental immunology, therapeutics, signalling and genetics, will identify how immune and inflammatory responses are controlled in both health and disease. The major outcomes of this work will be the generation of new knowledge, concepts and approaches to diagnose, prevent and treat the major human health problems of autoimmune diseases, inflammation, allergy and immunodeficiency.