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Dissecting Human B-cell Function: From Primary Immunodeficiencies To Chronic Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Despite knowing a lot about immunity in a mice, functional analysis of the human immune system has been a major challenge. I will study defects of immune cells in humans with gene mutations that cause an antibody deficiency. With new insights from these unique clinical samples, I will functionally dissect human immune responses, directly translate these to chronic inflammatory disease, and provide implications for future vaccine development and cancer treatment.
Understanding the immune response is proving extremely complex and promising results for disease treatments from animal models are often difficult to translate to new clinical therapies. My research is unearthing weaknesses in our current knowledge of the immune system and seeking to replace them with a foundation that can exploit new developments in computer modelling and systems biology. In this way I aim to rationally manipulate the immune response.
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
Defining The Requirements For Effective Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
The immune system rapidly responds to infectious pathogens to eradicate such microbes and limit the damage they can inflict upon the host. Individuals with primary immunodeficiencies have defects in the development and/or function of the cells of their immune system and are more susceptible to infectious diseases. This study will investigate such individuals to identify functions for specific genes and immune cells in order to understand the requirements for generating effective immune responses ....The immune system rapidly responds to infectious pathogens to eradicate such microbes and limit the damage they can inflict upon the host. Individuals with primary immunodeficiencies have defects in the development and/or function of the cells of their immune system and are more susceptible to infectious diseases. This study will investigate such individuals to identify functions for specific genes and immune cells in order to understand the requirements for generating effective immune responses.Read moreRead less
Control Of Pathogenic Antibody Responses In Humans
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Deficient or inappropriate antibody responses are at the core of many autoimmune diseases, allergies, food intolerances, and often explain the failure of vaccination strategies. Specialised follicular T cells control the quality of antibodies produced by B cells. This fellowship will combine basic studies investigating B cell helper or regulatory follicular T cells in humans with genetic studies identifying the causes of autoantibody-driven diseases. The results will uncover targeted therapies.
The cell types of the blood, such as red and white blood cells, are produced in the bone marrow from a rare stem cell. The stem cell uses a handful of important master-regulatory genes that act in a hierarchy to promote the blood cell differentiation process. This research aims to understand how these master-regulators function in isolation and together in producing the white blood cells that are required for our immune response to microbes, vaccination and to prevent cancer.
I am an immunologist focusing on understanding how can we combat chronic infections while preventing autoimmunity. This proposal aims to investigate how a poorly understood subset of lymphocytes called Tfh cells are regulated to promote the formation of protective antibodies, and prevent development of harmful antibodies that go on to cause or exacerbate diseases such as lupus, rheumatoid arthritis and type 1 diabetes. Our discoveries will illuminate novel drug targets for these diseases and hel ....I am an immunologist focusing on understanding how can we combat chronic infections while preventing autoimmunity. This proposal aims to investigate how a poorly understood subset of lymphocytes called Tfh cells are regulated to promote the formation of protective antibodies, and prevent development of harmful antibodies that go on to cause or exacerbate diseases such as lupus, rheumatoid arthritis and type 1 diabetes. Our discoveries will illuminate novel drug targets for these diseases and help generate more potent vaccines.Read moreRead less
Targeting Host Pathogen Interactions And Signalling Networks To Promote Death Of Infected Cells And Facilitate Pathogen Clearance
Funder
National Health and Medical Research Council
Summary
Preclinical models of infectious diseases including hepatitis B, HIV, tuberculosis and human herpes virus infections will be used to understand how pathogens interact with host cells. With this understanding we aim to identify which host cell signalling pathways play a critical role in limiting or faciliating pathogen persistence. After identifying the important cellular pathways we aim to target these host cell signalling components with clinical stage drugs to promote pathogen clearance.
DNA damage response pathways play important roles in preventing the onset of cancer and regulating the clinical response to chemotherapeutics, and some of the relevant proteins have additional functions during normal development. This fellowship will study new a human protein with key roles in the formation of the lung, and its roles in preventing devastating consequences of normal oxidative damage to DNA, as well as additional fundamental mechanisms involved in preventing genome mutations.
Defining The Cellular Interactions For Initiation And Maintenance Of Immunity To Intracellular Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
This immune system provides our body’s defense against invading organisms like viruses, preventing disease and maintaining health. Immunity involves the interaction of several different cell types that together form arsenals tailored to combat each different infection. Professor Heath will investigate how cells of the immune system orchestrate effective immune responses to viral infections and malaria. He will use this understanding to design novel approaches to vaccination.