Role For Sphingosine Kinase-1 In Endothelial Progenitor Cell Survival And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$294,205.00
Summary
Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand th ....Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand the process whereby mature endothelial cells are formed and how replacement of damaged endothelial cells is normally achieved. Stem cell therapy is considered the new frontier for the treatment of many diseases. Understanding how endothelial progenitor cells differentiate to mature endothelial cells and the signals which operate inside the cell may allow therapeutic manipulation of key target moecules in order to limit or control inflammation, tumourigenesis, rheumatoid arthritis and diabetic retinopathy. Our results suggest that one target maybe the enzyme sphingosine kinase.Read moreRead less
The Molecular And Cellular Trajectories Of Clonal Dendritic Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$826,742.00
Summary
Dendritic cells (DCs) are a blood cell type with a crucial role in our immune system. They are made in the bone marrow from stem and progenitor cells. How each of these cells individually makes DCs is complex and dynamic. We seek to understand this using cutting edge technologies to track each cell’s step-by-step role in this important process. This knowledge may help the use of DCs in the treatment of several diseases including autoimmunity and cancer.
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
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.
Investigating B Cell Development, Maintenance And High-affinity Antibody Production By ENU Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
B cells are essential for the protection against infections. This application aims to identify new genes that are crucial for the development or function of B cells and will investigate how mutations in newly discovered genes contribute to defects in the development and function of B cells and the pathogenesis of B cell leukaemia.
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.
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.
Extracellular Cues Compete With TCR Signalling To Alter Lymphocyte Polarity, Fate And Function.
Funder
National Health and Medical Research Council
Funding Amount
$509,954.00
Summary
Following an infection, our immune system generates a large and diverse repertoire of cells required to mount and regulate an appropriate immune response. The signals that control the different types of immune cells that develop, and how bacteria and viruses influence immune cell development, are not fully understood. This project will investigate the regulation of immune cell development, and how competing signals from infectious agents influence this process.
Dendritic cells (DCs) are the body’s sentinels, with three specialized subtypes. They monitor for infections and cancer and then activate immune T cells to clear it. Interestingly, they can all arise from a single cell, but the precise steps are unknown. By literally filming this process and analyzing the movie, we hope to draw the ‘family trees’ that lead to their generation. This knowledge will offer crucial clues as to how to boost or reduce their numbers for medical applications.
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.