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.
Identification Of Haematopoietic Stem And Progenitor Cell Subpopulations
Funder
National Health and Medical Research Council
Funding Amount
$873,525.00
Summary
We want to dissect the machinery underlying how each and every individual stem and progenitor cell generates the different blood cell types. We have at our disposal the latest molecular and computational technologies to do this. Knowledge gained from this project could be used for tissue engineering to make blood cells on demand for patients with immune deficiency, or alternatively to treat leukaemia patients where blood cells are overproduced.
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.
Mechanism Of Leukaemia Suppression By The Transcription Factor Ikaros
Funder
National Health and Medical Research Council
Funding Amount
$655,630.00
Summary
A subset of acute lymphoblastic leukaemias are characterised by mutations in the Ikaros gene. These leukaemias respond poorly to chemotherapy and require novel therapeutic approaches. We have discovered a new function of Ikaros in regulating leukaemia cell death. This project investigates how Ikaros regulates cell death and whether this is a general mechanism. Understanding Ikaros function is a step toward improved treatments for this aggressive type of leukaemia.
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.
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.
The Regulation Of IgE Antibody Production By Antigen-specific B Cells
Funder
National Health and Medical Research Council
Funding Amount
$454,105.00
Summary
Asthma and other allergies are caused by the inappropriate production of IgE antibodies by the immune system. IgE is not produced in response to most infections but the controls that normally prevent IgE production are unknown. We have identified two separate molecules that prevent IgE production during immune responses. In this proposal we aim to investigate how these controls work. This information may help to devise strategies for controlling IgE production and therefore allergic disease.
The Role Of The Homeobox Transcription Factor Hhex In Haematopoiesis And Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$623,112.00
Summary
We have shown that the Haematopoietically expressed homeobox (Hhex) protein plays important roles in development of immune cells. In addition, Hhex is required for development and maintenance of Acute Myeloid Leukemia (AML). This project will further investigate the requirement of Hhex in human AML, potentially identifying a new therapeutic target in this poor-prognosis cancer subtype. In addition, we will identify critical cofactors and targets of Hhex, revealing new therapeutic strategies.
The Role Of CCR6 In IL-17-producing CD8+ T Lymphocyte Activation And Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$514,041.00
Summary
T lymphocytes play an important role in the control of infection, but can also contribute to diseases such as autoimmune disease and cancer. This research will identify the function of a new subtype of T lymphocyte and determine whether inhibiting its function prevents disease.
Identification Of E-protein Complexes Controlling Natural Killer Cell Fate And Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$683,742.00
Summary
Diverse immune cell types are essential for effective broad-spectrum immunity. Master regulators control this diversity and have a well-characterized role in the development of antigen-specific immunity. In contrast, we lack mechanistic understanding of how master regulators control antigen-unspecific, innate immunity. Understanding the mechanism behind this will explain how diverse white blood cells can develop and reveal strategies to skew their development to improve immunity in humans.