The Mechanism For Combined Immunodeficiency And Autoimmunity Due To STK4-deficiency And Its Broader Application To Human PIDs
Funder
National Health and Medical Research Council
Funding Amount
$648,371.00
Summary
Why do some patients develop autoimmune diseases such as lupus where the immune system makes antibodies that attack its own body? To answer this, we plan to study a disease where a gene responsible for making antibodies is defective. Patients with mutations in the STK4 gene are unable to regulate the selection processes by which only the right cell is chosen to make antibodies. Understanding how STK4 works may help us unlock the mystery of what causes lupus.
Determining The Unique Processes That Control Memory B Cell-mediated Secondary Antibody Responses
Funder
National Health and Medical Research Council
Funding Amount
$853,644.00
Summary
Vaccines educate the immune system by training memory cells to make neutralizing antibodies when it re-encounters the pathogen. However, where and how these memory cells are activated in the secondary antibody response in immune animals remain unknown. Here we use cutting edge technologies to fate map and gene profile memory cells and determine the molecular switches that control the secondary antibody response. This will be complemented by human vaccine studies.
IL21, B-cell Proliferation And The Mechanism Of Memory Formation
Funder
National Health and Medical Research Council
Funding Amount
$981,896.00
Summary
Our immune system can ‘remember’ old infections, which is why we do not suffer from the same pathogen multiple times and why vaccines work. Much of this protection is due to memory B-cells, of which there are different kinds. We think the different memory B-cell subsets have different functions and understanding how they are made and how this is controlled will help us improve responses to critical infections – HIV, Flu – and in critical patient groups – aged people and transplant recipients.
The Control Of Autoimmunity Originating From Somatically Hypermutated B Cells
Funder
National Health and Medical Research Council
Funding Amount
$530,337.00
Summary
Our immune systems are capable of producing long-lived antibodies that can last a lifetime. Sometimes, this powerful process can however become abnormal and result in autoimmune diseases such as lupus. We have recently developed the first experimental mouse model that allows researchers to study this process in great detail. This funding will extend our initial observations by identifying the exact mechanisms by which important regulators of autoimmune disease act.
Neural Circuits For Active Vision In The Primate Cerebral Cortex
Funder
National Health and Medical Research Council
Funding Amount
$632,938.00
Summary
This project will try to understand how we use visual information to identify objects by their shape and motion, in natural situations in which the eyes are moving all the time. This will be accomplished by recording the electrical activity of brain cells while a trained animal is performing different types of tasks, such as tracking a moving object or exploring a scene with its eyes.
In this project, we will determine how a protein called ACKR4 suppresses antibody production and determine whether inhibiting its function will enhance the effectiveness of vaccination.
The Roles Of The Transcriptional Regulators Id2 And Id3 In Plasma Cell Differentiation And B Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$438,951.00
Summary
Antibody producing cells and memory B cells are crucial to successful vaccination and provide protection against infections. Development of both is controlled by factors that regulate gene activity, but the same factors are also involved in the development of blood cancers. Using new research tools and assays we will uncover the roles of the Id and E protein family of factors implicated in these processes, which may help in the design of new vaccination strategies and the treatment of blood canc ....Antibody producing cells and memory B cells are crucial to successful vaccination and provide protection against infections. Development of both is controlled by factors that regulate gene activity, but the same factors are also involved in the development of blood cancers. Using new research tools and assays we will uncover the roles of the Id and E protein family of factors implicated in these processes, which may help in the design of new vaccination strategies and the treatment of blood cancers.Read moreRead less
Positive And Negative Selection In The Germinal Centre Reaction
Funder
National Health and Medical Research Council
Funding Amount
$1,289,965.00
Summary
We will investigate the processes that control the production of antibodies by the immune system. In particular, we will determine how the immune system is normally prevented from producing autoantibodies that target the body's own cells and how this fails in the case of autoimmune diseases such as lupus. Targeted studies of a new type of "rogue" white blood cell we have identified will also provide important clues on how autoantibody-producing cells escape and cause autoimmune disease.
The Regulation Of IgE Antibody Production By Antigen-specific B Cells
Funder
National Health and Medical Research Council
Funding Amount
$454,105.00
Summary
Asthma and other allergies are caused by the inappropriate production of IgE antibodies by the immune system. IgE is not produced in response to most infections but the controls that normally prevent IgE production are unknown. We have identified two separate molecules that prevent IgE production during immune responses. In this proposal we aim to investigate how these controls work. This information may help to devise strategies for controlling IgE production and therefore allergic disease.
Functional Anisotropies In The Processing Of Orientation And Direction-of-motion By Human Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$366,164.00
Summary
We will study patterns of activity in the human brain to identify the cortical signature of normal visual function. The correspondences between patterns of brain activity and the structure and motion of the visual image in the normal human brain will provide data against which brain activity in a range of disorders from amblyopia to schizophrenia can be assessed.