Defining The Roles And Targeting Interferon-epsilon As A New Therapy For Influenza In Asthma And COPD
Funder
National Health and Medical Research Council
Funding Amount
$905,904.00
Summary
Influenza is a major cause of illness and death, especially in people with asthma and emphysema. There are issues with vaccines and current treatments are poorly effective. Effective treatments are urgently required. We have found a new immune factor, interferon-epsilon that is induced and used by influenza viruses to cause infection. We aim to understand how this occurs and to test new treatments for influenza that suppress interferon-epsilon, in healthy and susceptible individuals.
Targeting Disease-initiating Cells In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$477,170.00
Summary
The myeloproliferative neoplasms (MPN) are a related group of blood disorders. Despite the advent of targeted therapies, patients have significant ongoing morbidity, mortality and financial cost. A key reason underlying the persistence of disease is the presence of a stem cell pool that is resistant to targeted therapy. Clinical data has suggested that interferon may target these disease stem cells. We propose to use in vivo, validated disease models to investigate the role of interferon in MPN.
Tumour Induced Innate Immune Responses That Control Breast Cancer Metastases
Funder
National Health and Medical Research Council
Funding Amount
$596,164.00
Summary
The mechanisms of breast cancer spread to bone are largely unknown. We have found that cross-talk between tumour cells and the immune system exists to induce anti-tumour immune responses. By decreasing the release of proteins known to activate immune responses (type I interferons), tumour cells can hide from such responses and spread to tissues such as bone. We aim to identify the immune responses activated by type I IFN and if restoration of these pathways can block breast cancer spread to bone ....The mechanisms of breast cancer spread to bone are largely unknown. We have found that cross-talk between tumour cells and the immune system exists to induce anti-tumour immune responses. By decreasing the release of proteins known to activate immune responses (type I interferons), tumour cells can hide from such responses and spread to tissues such as bone. We aim to identify the immune responses activated by type I IFN and if restoration of these pathways can block breast cancer spread to bone.Read moreRead less
Type I Interferon Signalling In Bacterial Infection
Funder
National Health and Medical Research Council
Funding Amount
$738,274.00
Summary
Infectious diseases are a leading cause of death in Australia. Activation of disease-fighting inflammasomes sets in motion rapid immune defenses against pathogens. In this project, we explore how cell-cell communication molecules known as type I interferons communicate with inflammasomes to achieve the best outcome in the body in response to deadly bacterial infection. Understanding how these signals communicate with one another could reveal new ways to fight infectious diseases.
Understanding Neuroinflammation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,043,216.00
Summary
This project opens a new line of enquiry into the cellular signalling mechanisms involved in the progression of AD and establishes whether targeting the involvement of type-1 IFN signalling influences the evolution of AD. New and novel approaches are clearly required to treat AD. Importantly, we believe that neuroinflammation is common to all causes of dementia and targeting the neuroinflammatory pathways has much wider implications than targeting the primary causative pathway.
Clinical Implications Of IL7R Genotype: From Disease Risk To Disease Management
Funder
National Health and Medical Research Council
Funding Amount
$627,765.00
Summary
We’ve identified a genetic test (IL7R?) that may predict and prevent the risk of patients (i) failing to respond adequately to treatment for HIV (ii) who are at high risk of death after bone marrow transplantation and (iii) who fail to respond to interferon treatment for MS. This project aims to confirm these in very large patient groups and uncover the cellular basis for the genetic effect. Our goal is to provide a novel test that will improve patient outcomes in 3 serious disease states.
Defining The Role Of RNA Editing In Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$628,945.00
Summary
We are seeking to understand how red blood cells are produced. We have identified that a process called RNA editing may be important in the regulating the production of red blood cells.
The Role Of Apoptotic Caspases In Regulating Type I Interferon Production
Funder
National Health and Medical Research Council
Funding Amount
$791,746.00
Summary
Type I interferons (IFNs) are potent anti-viral cytokines. Dysregulated type I IFN responses result in major pathologies, e.g., embryonic lethality and defects in tissue homeostasis. We have identified a novel molecular mechanism regulating IFN production that relies on the host’s own apoptotic caspases. We hypothesize that apoptotic caspases critically regulate IFN responses during the process of cell death, with implications for tissue homeostasis and host responses to infection.
Dissecting In Vivo Cellular Responses To Interferons In Pathogen-infected Hosts
Funder
National Health and Medical Research Council
Funding Amount
$479,694.00
Summary
Tuberculosis (TB) is caused by virulent bacterium Mycobacterium tuberculosis and is a leading cause of death worldwide. Mechanisms underlying host resistance to the pathogen are poorly understood. Using a novel reporter mouse, the function of interferons in Mtb infection will be defined in vivo by tracking the cytokine-responsive cells. This will increase our understanding of the effects of these important cytokines in vivo, and could provide new candidate biomarkers for TB diagnosis.
Viral Targeting Of STAT Proteins: Roles In Disease
Funder
National Health and Medical Research Council
Funding Amount
$536,985.00
Summary
The capacity of viruses to evade the host immune response is critical to the development of disease. We recently showed that interaction of specific viral proteins with host immune proteins called STATs is vital to lethal disease caused by lyssaviruses. In this project, we aim to define in detail the functions of these interactions in viral modification of host biology and evasion of the immune response, and to use this information to develop new vaccines against highly pathogenic human viruses.