This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood cells called MAIT cells. MAIT cells are abundant in humans yet poorly understood. A better understanding of how these cells are regulated, and how they can be targeted in diseases, is necessary if we want to ultimately use these cells for immunotherapy.
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
Memory CD4 T Cells That Harbour The Reservoir Of Latent HIV Infection: Their Antigen Specificity, Function And Frequency Of Antigen-drivien Reactivation
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Current antiretroviral therapy for HIV-1 infection is able to suppress viral replication, but cannot eradicate it completely. Upon cessation of antiviral therapy, viral recrudescence is prompt, and most likely arises from latent reservoirs of HIV in various cellular compartments. The aim of this research is to characterise which subsets of CD4 T cells that are the target of HIV infection harbour HIV infection, including describing their function and individual target antigen specificities.
Building A Bridge Between Animal Models Of Blood Transfusion And Clinical Practice: Development Of Sheep Laboratory Models To Investigate The Effects Of Transfusion
Funder
National Health and Medical Research Council
Funding Amount
$86,117.00
Summary
This research project aims to develop clinically-relevant sheep laboratory models of transfusion that will provide a ‘bridge’ between human laboratory and sheep in vivo models and clinical setting by contributing to a better understanding of the underlying mechanisms of transfusion with stored blood products. Ultimately, addressing key knowledge gaps regarding transfusion of aged and cryopreserved blood products will result in improved outcomes for patients.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100106
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
An advanced flow cytometry facility for the Peter Doherty Institute. The establishment of a flow cytometry facility in the new Peter Doherty Institute for Infection and Immunity will enhance capacity to investigate immunity to a broad range of very serious diseases. This project will support researchers studying viral and bacterial infection as well as cancer and autoimmunity.
Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal c ....Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal cellular differentiation is crucial. The studies outlined here aim to contribute to the understanding of the these processes and hence help to provide the framework for future studies aimed at more directly altering cell fate decision for clinical applications. Read moreRead less
The Molecular Identification Of FoxP3 +ve Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$483,273.00
Summary
The immune system has a series of checks and balances in place to distinguish foreign bodies from normal, or self-antigens. In healthy individuals this prevents the immune system from attacking the cells and tissues of the body, food proteins, and the beneficial bacteria of the gut. However in autoimmune disease the system becomes imbalanced, allowing reactions to benign antigens, causing diseases such as diabetes, asthma and rheumatoid arthritis. One of the key players in the maintenance of a h ....The immune system has a series of checks and balances in place to distinguish foreign bodies from normal, or self-antigens. In healthy individuals this prevents the immune system from attacking the cells and tissues of the body, food proteins, and the beneficial bacteria of the gut. However in autoimmune disease the system becomes imbalanced, allowing reactions to benign antigens, causing diseases such as diabetes, asthma and rheumatoid arthritis. One of the key players in the maintenance of a healthy immune system is a specialized set of T cells known as T Regulatory cells. These cells are rare, at 1-4% of all T cells, yet are potent modulators of other T cells, and can prevent the activation of a T cell if it is reacting to a self-antigen. If they can control the cause of autoimmune disease, and patient Treg cells can be manipulated, it may be possible to use them therapeutically. Recently the switch that is required to generate regulatory cells was identified from patients with a rare autoimmune disease called Immunodysregulation, polyendocrynopathy, enteropathy, X-linked syndrome or IPEX. A mouse disease, Scurfy, with similar symptoms, is caused by the same mutations. The mutated gene encodes a protein, FoxP3, and this protein is able to bind to other genes in T cells and regulate their function. Without this protein, there are no T regulatory cells, resulting in autoimmune disorders. At this time there is very little known about how the FoxP3 gene is able to make a T cell become a regulatory T cell, and nothing is known about the genes that are turned off and on to facilitate this. If we can understand better the role of this protein, FoxP3, in the generation and maintenance of T cells with regulatory function, we may better be able to diagnose and treat autoimmune diseases, and this knowledge will have broad application to many autoimmune disorders.Read moreRead less