Identification Of Interferon Stimulated Genes That Limit HCV Replication And Predict Therapeutic Outcome
Funder
National Health and Medical Research Council
Funding Amount
$389,224.00
Summary
The only treatment for hepatitis C is Interferon-ribavirin combination therapy. Interferon works by stimulating the liver cells to produce antiviral proteins that can control hepatitis C virus replication, however we do not know which proteins are responsible. The aim of this proposal is to identify those proteins that can limit HCV replication using both a laboratory based and clinical approach and to identify markers that will predict treatment outcome.
Functional Significance Of Subcellular Localisation Of Viral 3C Protease In Rhinovirus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$613,513.00
Summary
Rhinovirus (RV) infections are the major cause of virus induced asthma attacks and common colds, causing significant morbidity and mortality. The incidence of asthma is increasing worldwide with new strategies urgently needed to reduce RV-associated disease. We have observed RV 3C protease in the nuclear compartment of infected host cells and propose to determine its significance in RV pathogenesis with relevance to asthma therapies.
Determinants Of CTL Recruitment Into The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$474,647.00
Summary
The size of CD8+ T cell (CTL) responses is central to their efficacy in virus control, and can be substantially influenced by how effectively they are recruited and expand after infection. This study will determine the impact of both CTL characteristics and antigen abundance on CTL recruitment and expansion after infection. Understanding the nature of these influences will enable a more informed approach to the clinical manipulation of CTL responses.
Immunopathological Role Of Monocyte-macrophages In Flavivirus Encephalitis.
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
Viral encephalitis is a life-threatening infection of the brain for which there are no reliable treatments. White cells called monocytes enter the brain from the blood and although important in the immune response that destroys the virus, can also damage the brain. Our work focuses on determining how monocytes migrate into the brain in viral infection, what functions they have once inside the brain, and how to exclude a certain types of monocytes that we have found to be particularly damaging.
Regulating Interferon Signalling In Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$547,428.00
Summary
Our innate immune system evolved as the front line defence against infection. However an uncontrolled response can lead to serious diseases such as septic shock, chronic inflammation as in hepatitis, autoimmune diseases such as systemic lupus erythematosus. The immune respnse is regulated by important hormones such as interferon produced by the body in these situations. This project aims to understand the negative or inhibitory mechanisms that prevent dangerous side effects of interferons withou ....Our innate immune system evolved as the front line defence against infection. However an uncontrolled response can lead to serious diseases such as septic shock, chronic inflammation as in hepatitis, autoimmune diseases such as systemic lupus erythematosus. The immune respnse is regulated by important hormones such as interferon produced by the body in these situations. This project aims to understand the negative or inhibitory mechanisms that prevent dangerous side effects of interferons without restricting their postive or beneficial effects. We will examine the actions of a molecule called the Suppressor of cytokin Signaling 1 (socs1) which we have recently discovered to modulate the actions of interferon in the mouse. Initially our studies will determine which molecules SOCS1 binds to inside a cell and the consequences for cell activation pathways. The next step will be to specifically block this interaction in the mouse and determine the effects on models of viral infection and inflammatory disease. The outcome of these studies will be a better understanding of how the body fights disease via the immune response and potential new approaches to develop therapeutic drugs.Read moreRead less
Molecular Characterisation Of Host Cell Targets Of Human Pathogenic Viruses And Evaluating Their Potential As Novel Therapeutic Targets.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed t ....There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed therapeutics against these deadly pathogens.Read moreRead less
I work on the molecular mechanisms of innate immunity. Priorities of my work are the immune response to pathogens such as viruses and bacteria and to cancer.
We seek to gain a detailed understanding of how interactions between the West Nile virus proteins and host factors involved in the IFN response determine the outcome of virus infection. Better understanding of the mechanisms employed by this highly pathogenic virus to disable the mammalian host's IFN response will have wider implications for our understanding of other human diseases such as cancer, autoimmunity and provide new avenues for design of efficient antiviral and anticancer therapies.
Molecular Characterization Of Dengue Virus Fusion And Antiviral Inhibitors.
Funder
National Health and Medical Research Council
Funding Amount
$573,557.00
Summary
Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries around the world, including Australia. Infection with dengue viruses cause severe and sometimes fatal disease. This proposal focuses on the way dengue virus enters cells and the development of drugs that will prevent virus entry. We have already identified compounds that inhibit the entry process of dengue into cells and this project will significantly build on these early findings.