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
Structure And Composition Of The Pre-T Cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
In order to recognize a wide variety of pathogens, humans produce many different T cell receptors (TCRs) by the process of gene-rearrangement. However, gene-rearrangement may not always lead to a functioning TCR. We are studying the pre-TCR protein that is responsible for monitoring the success of gene-rearrangement and is thus essential for the formation of a robust immune system. Understanding pre-TCR function will lead to new treatments for immune related diseases.
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.
This application proposes to study in detail the main target cell for HIV infection, namely CCR5+ CD4 T lymphocytes. After 30 years of the pandemic, fundamental knowledge of these cells, such as locations in the body, differentiation from other lymphocytes, and survival, is still lacking. These attributes determine whether or not they will be infected by HIV, whether this can be prevented by vaccines or CCR5 blocking drugs, and whether their long-term survival results in an inability to eradicat ....This application proposes to study in detail the main target cell for HIV infection, namely CCR5+ CD4 T lymphocytes. After 30 years of the pandemic, fundamental knowledge of these cells, such as locations in the body, differentiation from other lymphocytes, and survival, is still lacking. These attributes determine whether or not they will be infected by HIV, whether this can be prevented by vaccines or CCR5 blocking drugs, and whether their long-term survival results in an inability to eradicate HIV.Read moreRead less
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
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.
CD8+ T cells provide us with protection against viruses and can also mediate potent anti-tumour effects. Understanding the signals that initiate and sustain an effective CD8+ T cell response is important if we are to intervene in diseases where CD8+ T cell function is defective. We will study patients with inherited gene defects that disrupt some of the signals that T cells receive to determine the role those signals usually play in instructing CD8+ T cells to fight viral infection.