The Role Of Noncoding Subgenomic Flavivirus RNA In Virus-host Interactions
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Flaviviruses such as Dengue, Japanese encephalitis , and West Nile are major human pathogens causing more than 50 million infections per year. Elements in viral genome responsible for pathogenesis of these viruses are not well defined. Recently we have identified a unique for these viruses noncoding subgenomic flavivirus RNA (sfRNA) and showed that it is contributing to viral pathogenesis. In this proposal we aim to determine mechanisms by which sfRNA facilitates viral pathogenesis.
This project investigates the way in which viruses are able to use host cell machinery to make viral proteins and to replicate their own genetic material. We focus on the picornavirus family that cause illnesses with important health and economic consequences including serious heart infections such as myocarditis and pericarditis as well as the "common cold". This research we will reveal new possible avenues of antiviral development.
The Role Of Noncoding Viral RNAs In Flavivirus Infection And Exosomal Signalling
Funder
National Health and Medical Research Council
Funding Amount
$683,447.00
Summary
The application is aimed at investigating the novel role for viral noncoding RNAs in exosomal antiviral signalling and associated outcome of infection with West Nile virus. We will identify host enzymes involved in generation of viral noncoding RNAs, determine which host proteins they interact with and how these interactions determine their incorporation into secreted exosomes to influence outcome of infection.
Viral And Host Factors Determining Outcome Of Zika Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$910,780.00
Summary
The proposal aims at identifying viral and host factors determining outcomes of infection with Zika virus, a significant mosquito-transmitted pathogen associated with debilitating neurological pathology in new-borne babies from mothers infected during pregnancy. We will use cutting edge methodologies and infections models to bring our understanding of Zika virus infection to unprecedented level. The results could also facilitate identification of targets for effective anti-viral therapy.
Host Genes Controlling Flavivirus Infection: New Insights And Application For Developing Highly Effective Kunjin Replicon-based Ebola Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$736,995.00
Summary
The applications is aimed at identifying new host genes controlling infection with West Nile virus and other medically important flaviviruses such as dengue and Japanese encephalitis. For this, we will use novel in vivo RNAi screening approach with virus libraries encoding artificial microRNAs (amirs) targeting whole mouse genome. We will then apply amiR technology to produce highly effective Kujniin replicon-based Ebola vaccine candidate that has shown promising results in trails in primates.
Molecular Basis For RIG-I Like Receptor Activation Of The Innate Immune Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$564,770.00
Summary
This project is to understand how proteins in the cell detect the presence of invading viruses, and pass on the message for the cell to produce defence molecules. The overproduction of these defence molecules can lead to inflammatory diseases. This research will help us to understand the process of the innate immune response in cells and how we might control it in disease states.
MRNA Surveillance In Human Genetic Disease: Molecular Determinants Of Nonsense-mediated MRNA Decay
Funder
National Health and Medical Research Council
Funding Amount
$371,275.00
Summary
In about 1/3 of inherited disorders the mutations introduce an abnormal stop signal into the gene so that cells risk producing truncated or erroneous proteins. To prevent this cells have developed control surveillance mechanisms called Nonsense Mediated mRNA Decay (NMD). We have found a new form of NMD and our studies are directed determining how this works in cells, which genes use this pathway, and the consequences of this for human genetic disease.
An unusual type of molecule, circular RNA, was recently discovered to be present in human cells, and to potentially affect the ability of cancer cells in invade and metastasise. We will investigate the interactions these circular RNA molecules have with other molecules, what functions they have, and how they affect cancer cell invasion and metastasis. This could potentially reveal new ways of intervening in cancer metastasis, leading to new therapeutic modalities for cancer patients.
Cell-specific Regulation Of The MicroRNA/RNAi Pathway
Funder
National Health and Medical Research Council
Funding Amount
$659,390.00
Summary
MicroRNAs are a group of molecules that are critical for controlling the activity of genes. They function in a diverse range of biological systems, such the brain and immune system. Although we know that these molecules are important, how they are made in cells is still poorly understood. Because these molecules have potential therapeutic applications, it is essential that we gain a precise understanding of their biology before we will be able to apply these to medicine.
The exciting field of small RNA research was the subject of the 2006 Nobel Prize in Medicine, and holds great potential in the diagnosis and prognosis of disease such as cancer. Recent clinical studies suggest that drugs inhibiting small RNAs called microRNA present novel therapeutic opportunities. By defining the non-specific effects of such drugs and investigating new avenues for their delivery, this project will secure the safe application of these drugs into the clinic.