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.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
Understanding And Modulating Hyperinflammation Caused By Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
In humans, highly pathogenic influenza A virus (IAV) infections can be fatal, as the disease is untreatable with available vaccine or anti-viral drugs. My fellowship aims to advance our knowledge of the mechanisms by which the immune system induces and regulates inflammation during IAV infection, which can be both helpful and detrimental in fighting the infection. This is critical for identifying and developing new therapies for severe IAV infections in the future.
Host Metabolism And Responses Contributing To Flavivirus Replication And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$592,772.00
Summary
We aim to determine how viruses affect the cells they infect, In particular how they can alter the metabolism and balance of lipids in cells and how this impacts the bodies capability to respond immunologically. We believe that by understanding these basic principles we can target ares fr antiviral therapeutic potential.
Viral gastroenteritis poses an enormous burden in public health and is an emerging problem due to the acute nature of the infection process. We aim to understand how our bodies react to infection with Noroviruses, in particular how our immune system is triggered and unfortunately avoided during an infectious episode. We also aim to determine how Noroviruses utilized host components and pathways to facilitate infection in the body.
The Role Of The Inflammasome In Modulating Disease During Influenza Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,979.00
Summary
Highly pathogenic influenza A virus (IAV) infections in humans are associated with high mortality rates. This project will provide global and fundamental insights into our understanding of why IAV often cause fatal disease. It will advance knowledge of the mechanisms by which the host and virus interact and elucidate how the host's immune system responds to the infection and modulates disease, to facilitate the development of improved treatments for severe IAV infections.
Stealth Liposomes And SiRNA For The Treatment Of Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$528,793.00
Summary
Respiratory infections caused by Influenza and Respiratory syncytial virus cause significant hospitalisations and deaths within the community. For example, RSV causes around 1000 hospital admissions of young children a year and there is no cure or vaccination. Therapies are limited and toxic. We will develop and test a novel therapy based on gene silencing to specifically target viral genes, and combine this with our novel drug delivery system for better treatment of these diseases.
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.
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.