The Opposing Genetic Networks Underlying Plasticity Of Humoral Responses
Funder
National Health and Medical Research Council
Funding Amount
$667,783.00
Summary
The immune system makes antibody to clear bacterial and viral pathogens. Specialised types of antibody are needed for different pathogens. This project will study genetic changes that determine the specificity of an antibody response. Regulation of these genes may prohibit production of antibodies and inflammatory mediators that attack the body rather than foreign pathogens. Understanding these processes will identify points of therapeutic intervention for patients with immune disorders.
I am a molecular-cell biologist investigating the genetic control of lymphocyte differentiation. I study the mechanisms of action of transcription factors expressed specifically in B cells that regulate B lymphocyte specialisation and function, that determine the ability of mature B cells to respond to signals from other cells or from invading pathogens, and that enable the differentiation of antibody-secreting cells, the effectors of the B cell lineage. I lead the commercialisation efforts of o ....I am a molecular-cell biologist investigating the genetic control of lymphocyte differentiation. I study the mechanisms of action of transcription factors expressed specifically in B cells that regulate B lymphocyte specialisation and function, that determine the ability of mature B cells to respond to signals from other cells or from invading pathogens, and that enable the differentiation of antibody-secreting cells, the effectors of the B cell lineage. I lead the commercialisation efforts of our research Program.Read moreRead less
This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� c ....This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� cells that can rapidly become antibodyproducing cells should the same infection occur again in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an antibody-producing cell, by studying the genes that are known to be required for the cells to form, or to do their work. We will study animals whose immune systems are under- or over-active, to find out what part of the antibody-producing process is faulty. Using this information, we hope eventually to be able to study diseases of antibody producing cells in humans (as occur in allergy, asthma, rheumatoid arthritis and leukaemia), to be able to identify the precise cause of the problem, and to suggest a therapy. This information may also be used to improve the outcome of vaccination where an enhanced antibody response is desired.Read moreRead less
Targeting Antigen To Clec9A On Dendritic Cell For Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$744,624.00
Summary
Dendritic cells capture infectious organisms and display them to other immune cells to initiate immunity. The process of capturing organisms requires dendritic cells to express a variety of cell-surface receptors that detect components carried by infectious agents. Here we will examine the efficacy of attaching vaccine components to a targeting agent that binds one of these receptors with the aim of enabling dendritic cells to efficiently kick-start immunity against vaccine components.
Mechanisms Controlling Antibody Production By Modulating B Cell Antigen Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$536,628.00
Summary
This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment, or resul ....This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment, or result in uncontrolled B cell accumulation in lymphoma, leukemia and myeloma. In order to develop rational, specific methods for treating these diseases, it is necessary to identify and understand the biochemical mechanisms that normally control antibody formation against infectious agents, self components, and innocuous environmental agents. The project focuses on defining the biochemical mechanisms by which the antibody-forming cells, B lymphocytes, sense infectious, innocuous, or self components. These cells carry specific receptors that bind these components and transmit signals into the B lymphocyte. The research will determine how different types of signal are transmitted by the receptor so that, normally, large amounts of antibody are made against infectious agents but very little antibody is made against self components, and that B cell accumulation is tightly limited. By identifying how the types of signals are changed, the results of this project will reveal control mechanisms that may be altered in autoimmunity, allergy, immune deficiency, or lymphoma, and that may be able to be used as drug targets to cure these diseases.Read moreRead less
Leptin As A Natural Regulator Of TFH Cell Differentiation And Vaccination Response
Funder
National Health and Medical Research Council
Funding Amount
$594,901.00
Summary
Follicular helper T (Tfh) cells constitute a CD4+ T cell subset that plays an instrumental role to support protective antibody responses in infection and vaccination. Although malnutrition is associated with poor vaccine responses and increased risks of infections, the mechanism is poorly understood. We will investigate the mechanism by which leptin, a hormone secreted by adipose cells, regulates Tfh cell function and vaccination response.
The Role Of Linked Cytokines In T Helper Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$390,504.00
Summary
An important class of T cells known as T Follicular Helper cells (TFH) orchestrate the immune response so that we can produce antibodies to fight infection. The novel finding that our Lab made last year is that the molecule interleukin 21 (IL-21) is a growth factor for TFH. The findings we have made thus far could be used in a number of ways. For eg, IL-21could be used to expand numbers of TFH, using them to boost vaccination or natural defences against viruses, bacteria and tumour cells.
Genetic And Molecular Mechanisms Dysregulating CD4 T Cell Tolerance In Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$575,947.00
Summary
This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemic ....This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that normally control T cell responses to self components, and how inherited defects lead these mechanisms to break down. The project focuses on defining how CD4 T cell regulation breaks down in a well established but poorly understood example of polygenic inherited susceptibility to autoimmune disease. Polygenic diseases are those where susceptibility is inherited in a complex way involving many different genes either acting together or in opposition, and the molecular basis for this kind of inheritance is particularly poorly understood. The project will analyse the basis for this kind of inheritance pattern by analysing the direct action of diabetes susceptibility genes at the level of the specific T cells responsible for autoimmune attack and in terms of the biochemical pathways within the T cells that are dysregulated. By identifying the mechanisms and biochemical pathways that are dysregulated in autoimmune disorders, the results of this project will concepts and targets for understanding and diagnosing autoimmune diseases and for developing new drugs or vaccines to prevent T cells damaging vital organs and cure these diseases.Read moreRead less