Soluble Inhibitors Of Influenza Virus In The Airway Fluids Of Mice, Ferrets And Humans.
Funder
National Health and Medical Research Council
Funding Amount
$404,803.00
Summary
This study will characterize the ability of soluble proteins in airway secretions to recognize and destroy influenza viruses. As many of our insights regarding influenza pathogenesis are derived from studies in animal models, we will characterize the importance of proteins in airway fluids from mice and ferrets, as well as from humans. These findings will be of particular importance when assessing the relevance of particular animal models to understanding human disease.
Determining The Clinical Effectiveness Of Antiviral Drugs Against Oseltamivir- And Laninamivir-resistant Influenza Viruses In Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$388,067.00
Summary
Currently, the neuraminidase inhibitors are the only drugs that are effective against seasonal influenza viruses. However, viruses can develop resistance to these drugs. Using viruses with varied levels of resistance, the project will determine the effectiveness of different drug treatments in animal models. This will lead to better treatment for those patients seriously ill with drug-resistant influenza viruses.
The Role Of The Interaction Of The CMV M11 Immune Evasion Molecule With CD44 In Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$457,500.00
Summary
Herpesviruses can cause infections that persist for the lifetime of the host. They have evolved many mechanisms to elude the host's immune response that would otherwise eliminate them. One memberof the herpesvirus family that is particularly adept at avoiding host immunity is cytomegalovirus. This virus, while not causing symptoms in healthy individuals, is a significant cause of disease and mortality in individuals with suppressed immune systems such as transplant and AIDS patients, and in the ....Herpesviruses can cause infections that persist for the lifetime of the host. They have evolved many mechanisms to elude the host's immune response that would otherwise eliminate them. One memberof the herpesvirus family that is particularly adept at avoiding host immunity is cytomegalovirus. This virus, while not causing symptoms in healthy individuals, is a significant cause of disease and mortality in individuals with suppressed immune systems such as transplant and AIDS patients, and in the fetus which has a poorly developed immune system. In the current project we will explore at a molecular level how a virus-encoded molecule called m11 interferes with the functions of a cellular receptor called CD44 that has a range of cell functions including cell migration, activation and proliferation and signal transduction. The interaction of m11 with CD44 modifies cell migration and is likely to affect cell activation. Defining how m11 mediates its affects will allow us to define strategies to develop potential antiviral therapies. As CD44 is also involed in contributing to a range of diseases where inappropriate inflammation develops it may be that m11, or derivatives of it, could be harnessed to ameliorate these inflammatory diseases.Read moreRead less
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.
A Humanised Mouse Model For Herpes Simplex Virus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$277,109.00
Summary
Herpes simplex virus (HSV) causes cold sores and genital herpes, diseases that persist and recur. This persistence is because HSV has several ways of stopping the body from detecting and eliminating the cells that it infects. This project will generate new tools that will help us to understand one of the ways that HSV hides from our defences and may be useful in developing immune-based therapies to treat the infection.
A Potent Anti-HIV-1 Gene Therapy Agent In A Humanised Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$1,147,139.00
Summary
We have shown that a synthetic protein called Nullbasic can protect human cells from becoming infected by the AIDS virus, HIV-1. In this project a gene therapy approach will be used to test if a human immune system modified to contain Nullbasic is protected from HIV-1 in an animal model.
The Balance Of Signals Received By NK Cells Is Modulated By Viruses As A Mean Of Immune Escape.
Funder
National Health and Medical Research Council
Funding Amount
$583,175.00
Summary
Cytomegalovirus (CMV) affects about 60% of the population in Australia. Infection is partially controlled by the immune system but CMV is never eliminated and people remain carriers for the rest of their life. Reactivation of CMV in healthy individuals is usually asymptomatic, but it causes severe diseases in people with immune deficiencies. We seek to discover the mechanisms used by CMV to escape immune surveillance, in order to gain insights into the development of improved antiviral therapies
Exploration Of The Role Of Microbes In Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$687,974.00
Summary
This fellowship will investigate diseases of the gastrointestinal tract of children. The research program will undertake a range of is a highly innovative projects including; development of an effective rotavirus vaccine to be administered to newborns; genetic characterisation of rotavirus strains able to escape vaccine protection; and how alterations in the human gut microbiome (bacteria and viruses) influence the development/relapse of CrohnÍs disease.
Molecular Mechanism And Therapeutic Implications Of Prion Disease Strain Types In Sporadic Creutzfeldt Jakob Disease.
Funder
National Health and Medical Research Council
Funding Amount
$345,634.00
Summary
The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an ....The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an abnormal disease associated form of the host prion protein. Differences in the duration of illness and pathology of sporadic CJD suggests that the disease may be caused by different prion strains. The existence of different prion strains may explain the limited clinical success of anti-prion therapeutics modeled in rodent models of prion diseases. In this study a cell-free model of prion propagation will be used to investigate the basis of human prion strains. This assay will also be used to identify and determine whether the therapeutic efficacy of anti-prion compounds is influenced by human prion strain type. This study will represent the first host species and prion strain specific screen of anti-prion therapeutics aimed at developing the best possible model for the identification and development of therapeutics for human prion diseases.Read moreRead less