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.
Defining The Roles Of The Chemotactic Receptor EBI2 For The Regulation Of Leukocyte Migration And The Generation Of Immunity
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
The proposed study aims at improving our understanding of the role of the immune cell receptor Epstein-Barr virus-induced gene 2 (EBI2) in guiding the movement of white blood cells during immune responses. The project will investigate the function of EBI2 in the control of infectious diseases and its regulation on human immune cells. These insights have the potential to create new therapeutic approaches to treat human autoimmune and inflammatory diseases and improve vaccine design.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
Coordinating Leukocyte Migration And Interaction During Immune Responses: The Multiple And Central Roles Of The Orphan G Protein Coupled Receptor EBI2
Funder
National Health and Medical Research Council
Funding Amount
$512,716.00
Summary
The ability of the immune system to fight infections relies on the capacity of immune cells to navigate within the body. This study aims at understanding the role of the immune cell receptor Epstein-Barr virus-induced gene 2 (EBI2) in guiding the movement and the interaction of the different types of white blood cells during immune responses. These insights will add to our understanding of immune cell migration thereby offering new therapeutic approaches to improve or control immune responses.
Role of antibodies and their receptors in chronic inflammation: The activation of inflammatory white blood cells is a major mechanism of tissue destruction in certain autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. It is well known that destructive chemicals, enzymes and hormones are released by these cells into affected tissues, for example joints and kidneys. What is lacking is knowledge of the earliest steps in the immune system that activate the inflammator ....Role of antibodies and their receptors in chronic inflammation: The activation of inflammatory white blood cells is a major mechanism of tissue destruction in certain autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. It is well known that destructive chemicals, enzymes and hormones are released by these cells into affected tissues, for example joints and kidneys. What is lacking is knowledge of the earliest steps in the immune system that activate the inflammatory white blood cells and drive this inflammation cascade to the point where chemicals are released and tissued destroyed. This project investigates the role of one of the major receptor families involved in the activation of inflammation. These are receptors for antibodies called FcR. The binding to these receptors of unusual antibodies produced in autoimmune disease initiate events that stimulate white blood cells leading to their activation and the secretion of inflammatory substances. Our work leading up to this project has been very exciting and has shown that one receptor in particular, FcgammaRIIa is unique to humans, is the most widespread FcR in the body and is the most potent activator of inflammatory substance release. We will be studying animal models to precisely define how this human receptor works. Mice have been generated which contain this uniquely human receptor and these mice develop many features of human autoimmune disease such as the joint destruction, kidney destruction and lung destruction seen in both rheumatoid arthritis and lupus. The principal aim of our study is to define the role of this human receptor in the development of inflammatory conditions with the ultimate goal of using this information to generate new treatments for these diseases.Read moreRead less