Using Single-cell Genomics To Resolve Functional Diversification By CD4+ T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$1,048,096.00
Summary
During immune responses, individual CD4+ T cells multiply and produce hundreds of descendants, with close relatives within a family often developing very different skills. How such differences emerge from one ancestor remains unclear. We use new methods to look at individual CD4+ T cells in unprecedented detail, allowing us to see how close relatives begin to grow apart. Using this, we hope to find novel ways of educating CD4+ T cells to prevent infectious and immune-mediated diseases.
Interleukin Signalling In CD4+ T Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$663,919.00
Summary
Our bodies rely on the production of antibodies to fight infection. The cytokine IL-21 is produced by immune cells called T follicular helper (Tfh) cells that help B cells make antibodies. Tfh cells, in turn, are controlled by regulatory (Tfr) cells. Our findings demonstrate that IL-21 supports Tfh cells and limits Tfr cells, thus favoring antibody production and long term immunity. Using genomic and cellular approaches, the mechanism(s) underlying these observations will be explored.
Elucidating Immune Responses By Single Cell Pedigree And Tracing Analysis
Funder
National Health and Medical Research Council
Funding Amount
$666,950.00
Summary
To develop vaccines and to combat autoimmunity, we need to understand how initial immune activation influences the fate of immune cells and their progeny. To achieve this, we have developed microscopic techniques and analytical software with which to observe how initial signalling processes in the parent immune cell influence the death, proliferation and differentiation of its daughters, granddaughters and further progeny. We will use these approaches to determine how immune cell fate is control
Asymmetric Cell Divison In T Cell Development: Consequences For Immunity And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$642,608.00
Summary
Human health depends upon the development of an immune system that can effectively control infection without damaging normal tissue. In this project, we assess a new paradigm by which immune cell development might be controlled, in which an immune cell precursor divides in such a way that its two daughters inherit different molecular constitutents that subsequently regulate the adoption of different cell fate. The likely consequences of this phenomonon on immunity and cancer will be explored.
Regulation Of T Cell Effector Function In Peripheral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$698,550.00
Summary
Protection from infections relies on different types of immune cells. While some of these cells are found in the blood, others reside in peripheral tissues such as the skin. We will analyse the function of these peripheral immune cells to understand how they work to fight off infections. We will also investigate how so-called memory cells that permanently reside in peripheral tissues can protect from re-infection with similar bacteria or viruses.
Identifying The Ontogeny And Fate Of T Follicular Helper Cells By Two-photon Photoconversion
Funder
National Health and Medical Research Council
Funding Amount
$623,070.00
Summary
The aim of this proposal is to investigate immune cells called T follicular helper cells using a novel microscopy-based method that we have developed. This method lets us ‘tag’ these cells in a way that enables us to distinguish them from all other cells and follow them as they migrate to different immunological compartments during the response. T follicular helper cells are important for protective immune responses against pathogens and a better understanding of this T cell subset will aid vacc ....The aim of this proposal is to investigate immune cells called T follicular helper cells using a novel microscopy-based method that we have developed. This method lets us ‘tag’ these cells in a way that enables us to distinguish them from all other cells and follow them as they migrate to different immunological compartments during the response. T follicular helper cells are important for protective immune responses against pathogens and a better understanding of this T cell subset will aid vaccine design.Read moreRead less
Characterisation And Development Of Type-2 NKT Cells
Funder
National Health and Medical Research Council
Funding Amount
$853,885.00
Summary
Humans defend themselves from foreign pathogens by mounting a protective immune response. Type-2 NKT cells recognise foreign lipid molecules and play a key role in immunity. This project is designed to understand to how Type-2 NKT cells develop within the body, how they recognise lipid molecules and how they carry out their immune functions. This work will have important implications in understanding the role of NKT cells in human health and disease.
Molecular And Cellular Control Of Human Th9 Cell Differentiation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$550,888.00
Summary
T helper 9 (Th9) cells are a recently defined population of CD4+ T cells that have been implicated in immunological disorders ranging from allergy, asthma, inflammatory bowel disease, and cancer, to host defence against fungal and parasitic infections. As such, Th9 cells are extremely important to human health and disease. This project aims to define the mechanisms involved in the generation, regulation and function of human Th9 cells.
Making Human T- And B-lymphocytes For Immunotherapy And Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$795,880.00
Summary
Lymphocytes are white blood cells that are involved in producing antibodies, killing defective cells, or killing cells infected with viruses. In recent years, researchers have found ways to harness lymphocytes to develop medicines for treating a variety of different cancers. In this project, we will establish methods to make human lymphocytes in the laboratory from stem cells, paving the way for the broader application of this cell type to new therapies.
The immune system must be tightly regulated to make sure that it makes the right response to effectively fight off infection whilst avoiding inappropriate responses that cause damage such as in autoimmunity, inflammation or allergy. This project studies patients who have genetic defects that affect their immune systems and make them susceptible to infection and/or harmful immune responses. This will reveal some of the critical signals that maintain immune control.