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.
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.
The Interplay Between Viperin, Peroxisomes And The Cellular Innate Antiviral Response
Funder
National Health and Medical Research Council
Funding Amount
$556,127.00
Summary
Infection with a virus initiates a cellular antiviral response that attempts to limit viral replication, however how this response is regulated is not well understood. In this proposal we will investigate a cellular protein (viperin) that can regulate this process by interaction with peroxisomes to amplify the antiviral response. This work will provide possible targets for therapeutic manipulation of the innate immune response that will be applicable to a wide range of viral infections.
Structure-function Of Type I Interferon Receptors: Informing The Basis For Selective Modulation Of Signal Transduction And Function
Funder
National Health and Medical Research Council
Funding Amount
$1,316,153.00
Summary
Interferons (IFNs) are a family of proteins with critical roles in infectious and inflammatory diseases and cancers. Currently we do not understand why there are so many type I IFNs, their different functions and how they are achieved. This project will determine at a fine molecular level how different IFNs interact with molecules on target cells and transmit particular signals. We will focus on a novel IFN? that we discovered. These studies will underpin the development of new therapies.
Interferon Epsilon, A Key Cytokine In The Pathophysiology Of The Female Reproductive Tract Mucosa
Funder
National Health and Medical Research Council
Funding Amount
$793,303.00
Summary
The female reproductive tract is a complex environment, which permits pregnancy but protects against infections, all under the influence of hormones and the resident microbial flora. We have discovered a novel protein called interferon epsilon that acts on cells in the female reproductive tract to regulate protection against infections. We aim to discover how this new protein works and will determine its therapeutic potential in infections and inflammatory diseases affecting women's health.
Investigation Of The Molecular Basis Of Human Nevogenesis And Melanoma Initiation
Funder
National Health and Medical Research Council
Funding Amount
$598,220.00
Summary
The number of moles and lifetime exposure to solar UV are the major risk factors in melanoma development. A genetic association between the IRF4 gene and mole number and melanoma susceptibility has been reported. We propose that changes in the function of this gene will impact on the behaviour of melanocytes/melanoma cells, their response to UV radiation and interaction with surrounding cells. Understanding the function of this gene will provide crucial insight into the initiation of melanoma.