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.
Protein-RNA interactions are critical in regulating the response to virus infections, and controlling the expression of genes involved in inflammation. Small interfering RNAs (siRNAs), important tools in gene discovery and potential therapy against virus infections and cancer, can activate the innate immune response. By understanding protein-siRNA interactions, we will gain new insights into the design of siRNAs for studying gene regulatory networks and for practical application in medicine.
Designer RNA-binding Proteins For Research And Therapeutic Purposes
Funder
National Health and Medical Research Council
Funding Amount
$557,480.00
Summary
It has become clear recently that ribonucleic acids play many roles in the switching on and off of genes in humans and other organisms. These molecules play roles in a number of diseases, including HIV-AIDS, hepatitis, and a large number of inherited disorders. We propose to build a library of protein molecules that can bind specifically to a wide range of RNA targets and modulate their function. These molecules have the capacity to act as therapeutics for a wide range of diseases.
Structural And Functional Characterisation Of The Killer Cell Immunoglobulin-like Receptor (KIR) Family Of Natural Killer Cell Receptors
Funder
National Health and Medical Research Council
Funding Amount
$348,070.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used to guide in the selection of bone marrow donors in the treatment of leukemias as well as understanding how we fight off infections.
A Structural Investigation Into The Adaptive Immune Response To A Persistent And Ubiquitous Human Virus
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
This proposal is focussed on understanding the precise shape of proteins that control the immune response to Epstein Barr Virus. EBV is an ubiquitous human pathogen that has been linked to a number of cancers. This research proposal will further our understanding of the immune response to EBV, which will lay the foundations for developing therapeutics against this disease.
Herpesviruses infect most Australians and cause recurrent ulcers, birth defects and cancer. Infection lasts lifelong, and spreads to close contacts without obvious clinical signs. Thus disease is hard to prevent. However we can learn much from related animal infections. We have shown that both mouse and human herpesviruses enter mice via cells in the nose. Thus human infections might follow the same route. We will define what body defences work here and whether vaccines can prevent infection.
Human ?-herpesviruses persist for life, cause cancers and emerge with particular virulence when the immune system is weak. Vaccination against them is therefore an important health priority. We have shown for a related ?-herpesvirus of mice that live vaccines protect. Antibody seems to play a major role. We will test whether safer, recombinant vaccines are also sufficient to elicit protective antibody. Thus we can establish a viable strategy for preventing virus-induced human cancers.