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.
Utilising Human Primary Immunodeficiencies To Study Lymphocyte Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$429,346.00
Summary
Human immunodeficiencies are diseases arising from naturally occurring mutations. In this instance, the specific genes mutated in the immunodeficiencies we study have been identified. However, it is unclear how defects in these genes make an individual manifest as an immune deficient state, rendering them vulnerable to disease. By studying immune cells from these individuals we hope to uncover the normal function of these genes and subsequently provide for new therapies for these conditions.
Understanding the immune response is proving extremely complex and promising results for disease treatments from animal models are often difficult to translate to new clinical therapies. My research is unearthing weaknesses in our current knowledge of the immune system and seeking to replace them with a foundation that can exploit new developments in computer modelling and systems biology. In this way I aim to rationally manipulate the immune response.
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.
Understanding the immune response is proving extremely complex and promising results for disease treatments from animal models are often difficult to translate to new clinical therapies. My research is unearthing weaknesses in our current knowledge of the immune system and seeking to replace them with a foundation that can exploit new developments in computer modelling and systems biology. In this way I aim to rationally manipulate the immune response.
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.
Roles Of ID2 In Regulating Critical Innate And Adaptive Arms Of The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$597,418.00
Summary
The immune system protects us from a wide range of pathogens and foreign invaders. Natural killer (NK) cells and T cells are an critical component of the immune system due to their ability to detect and kill virally infected and malignant cells. Our work will endeavor to understand the molecular steps essential for these cells to develop and become armed to ensure immune protection.
Regulation Of The Anti-tumour Immune Response By The Chemokine Decoy Receptor CCX-CKR
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Melanoma is a significant cause of cancer-related deaths in Australians. Death is usually due to metastasis of the cancer to the lungs and other organs. In this project, we will take advantage of unique mouse models to determine whether inhibition of the function of a novel protein can prevent melanoma growth and metastasis to different organs. The results of this study may lead to new therapeutic approaches to control malignant melanoma and other metastatic cancers.
Transcriptional Control Of Peripheral T Cell Differentiation During Pathogen Infection And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
White blood cells, specifically helper and killer T cells, play an important role in fighting infection. They are tightly regulated and if not properly controlled can lead to aggressive autoimmune diseases such as diabetes and multiple sclerosis. My studies will elucidate the mechanisms behind the regulation of T cells at steady-state and during disease. Insights gained from this project will have implications for the design of new approaches to combat infectious and autoimmune diseases.