A T Cell-Specific GR Promoter Determines Responsiveness To Glucocorticoids In Different Immune Compartments
Funder
National Health and Medical Research Council
Funding Amount
$417,500.00
Summary
Synthetic glucocorticoids, such as dexamethasone and prednisolone, are commonly used as potent anti-inflammatory steroid drug during the treatment of major human trauma and cancer. A side-effect of these very high steroid doses is a major down-regulation of the immune system, particularly massive death of important immune cells called T-cells, which can have a major impact on patient recovery and potential mortality. These T cells are particularly sensitive to glucocorticoid-induced cell death a ....Synthetic glucocorticoids, such as dexamethasone and prednisolone, are commonly used as potent anti-inflammatory steroid drug during the treatment of major human trauma and cancer. A side-effect of these very high steroid doses is a major down-regulation of the immune system, particularly massive death of important immune cells called T-cells, which can have a major impact on patient recovery and potential mortality. These T cells are particularly sensitive to glucocorticoid-induced cell death and have very high levels of receptors for these steroids called glucocorticoid receptors (GRs). We have discovered a unique GR gene promoter (designated 1A) that is active in T cells. Very little is known about how this gene promoter is regulated. This promoter may be a useful therapeutic target to block T cell death (caused by steroids) during recovery from injury, infection and cancer. Separation of anti-inflammatory and side-effects such as high T-cell death or blockade of these effects on T cells would have a major impact on patient immune status and recovery, and reduce the incidence of debilitating side-effects. Therapeutic down-regulation of this T cell-specific GR gene promoter could lead to targeted blockade of steroid-induced T cell death and help maintain a strong immune system. This application brings together a unique team of investigators (CIs) that have a strong history of collaboration in this area with recent publications in very high ranking international journals. The CIs bring a multi-disciplined approach combining endocrinology, molecular biology and cellular immunology to determine the underlying mechanisms of steroid actions and their effects on immune function. Both Dr Cole (CIA) and Dr Godfrey (CIB) have excellent track records in this area.Read moreRead less
Deciphering IFN Type III, TGF?, IL-10 And Adenosine Pathways In Natural Killer Cells: Enhancing The Innate Anti-metastatic Response Against Breast Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
This project will determine whether one or more factors produced in tumours (eg. cell hormones and metabolites) inhibits NK cells from controlling breast cancer spread using the best available mouse tumour models. We will use genetics to specifically delete response to these factors by NK cells. It is a completely novel approach and this information will allow for the more rational design of cancer treatments following surgery and local radiotherapy and/or chemotherapy.
Professor Godfrey is an immunologist with a long standing history as a pioneer in the study of a specialised type of white blood cell, known as NKT cells. NKT cells are activated in response to lipid-based molecules that are thought to alert the immune system, via NKT cell activation, to the presence of infectious agents or other abnormalities. A better understanding of how NKT cells function will provide new approaches to battling a broad range of diseases where these cells are implicated, incl ....Professor Godfrey is an immunologist with a long standing history as a pioneer in the study of a specialised type of white blood cell, known as NKT cells. NKT cells are activated in response to lipid-based molecules that are thought to alert the immune system, via NKT cell activation, to the presence of infectious agents or other abnormalities. A better understanding of how NKT cells function will provide new approaches to battling a broad range of diseases where these cells are implicated, including cancer, autoimmunity, allergy and infection.Read moreRead less
Determining Regulators Of ILC3 In Mucosal Barrier Function And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$705,209.00
Summary
Innate lymphoid cells (ILCs) are specialized cells that defend the body against invading microorganisms at the body’s surfaces, mediate pathogen clearance and tissue repair but may also drive inflammatory conditions such as allergic asthma and inflammatory bowel disease. We will investigate the molecular switches that regulate this novel cell type and potentially uncover novel molecules or pathways for therapeutic targets.
The Role Of Cytokines In Tumor-induced Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$754,473.00
Summary
Cancer-induced immune suppression is a major obstacle to the effective treatment of many cancers. We have shown that the cytokine IL-23, plays an important role in cancer initiation, growth and development. My project aims to characterize the cells that produce IL-23 in the cancer microenvironment and define how it suppresses cells of the immune system. A greater understanding of this cytokine’s mechanism of action will enable the rational improvement of treatments for patients with cancer
Induction Of Natural T-Regulatory Cells By Thymic Dendritic Cell Populations
Funder
National Health and Medical Research Council
Funding Amount
$413,775.00
Summary
In this study, we will determine the roles of the antigen presenting cells, namely denderitic cells, in the induction of T-regulatory cell (T-reg) developemnt in the thymus. T-reg cells play important roles in controlling the development of autoimmunity. This study will help to understand the possible causes of autoimmune diseases and to develop new treatments for these diseases.
Control Of Haematological Cancers By Natural Killer Cells
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Haematological cancers affect the blood and lymphoid organs and are generally lethal. Therapies targeting the anti-tumour capacities of the immune system have shown promising results in cancer patients. Natural Killer (NK) cells are key players of anti-tumour immune responses. This project will provide a better understanding of NK cell-mediated control of haematological malignancies that will be directly applied to the design of new curative therapies for blood cancer patients.
Understanding Immunosuppressive Pathways In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$419,178.00
Summary
Cancer-induced immune suppression is a major obstacle to the effective treatment of many cancers. Suppression can be mediated by cells of the immune system, or cancers themselves. My project aims to investigate 3 suppressive pathways and determine their hierarchy in different mouse models of cancer using mouse genetics and antibody-based treatment approaches. Understanding these processes ongoing in the cancer environment will allow the design of more effective cancer therapies.
The aim of this project is to develop mathematical models and computer software capable of predicting immune responses to infection and disease. This “artificial immune system” should lead to improved vaccine design and better understanding of what causes the immune system to attack its own body, causing autoimmune disease, or fail to respond, causing immunodeficiency. This enabling science could then lead to improvements in treatment for a range of conditions of clinical importance.
Diet And Mental Health: Translating New Knowledge Into Innovative Prevention And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
I have pioneered the development of a robust body of evidence demonstrating the important role of diet in mental health and I am now recognised internationally as a research leader in this new field. The next important step is to translate this knowledge into new prevention and treatment strategies in order to address the substantial global burden of illness attributable to mental disorders.