Studies On The Flavivirus Nonstructural Proteins And Untranslated Regions Of The Genome Involved In Virus Replication
Funder
National Health and Medical Research Council
Funding Amount
$244,277.00
Summary
Flaviviruses cause potentially fatal diseases of global importance such as yellow fever, Japanese encephalitis (JE) and dengue haemorrhagic fever. Flavivirus disease is also important in Australia with recurrent outbreaks of dengue fever, Australian encephalitis and more recently JE in the northern regions of the continent. Effective vaccines are only available to yellow fever and JE and tick-borne encephalitis and are either live or killed preparations which are potentially hazardous and costly ....Flaviviruses cause potentially fatal diseases of global importance such as yellow fever, Japanese encephalitis (JE) and dengue haemorrhagic fever. Flavivirus disease is also important in Australia with recurrent outbreaks of dengue fever, Australian encephalitis and more recently JE in the northern regions of the continent. Effective vaccines are only available to yellow fever and JE and tick-borne encephalitis and are either live or killed preparations which are potentially hazardous and costly to produce. There are no therapeutic agents (antivirals) available against flavivirus diseases. To produce safe and cost effective vaccines against flaviviruses and to identify targets for antiviral agents, a more complete understanding of how these viruses replicate in the cell and cause disease is required. This investigation aims to define specific aspects of the flavivirus life cycle that are currently unknown.Read moreRead less
NUCLEAR AND TRANSGOLGI TARGETING AND MEMBRANE INDUCTION BY DENGUE NS5 RNA-DEPENDENT RNA POLYMERASE INTERDOMAIN REGION
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
Dengue virus is the causative agent of a mosquito-borne disease, Dengue fever, relevant to northern Queensland, where antibodies from a previous infection can complex with virus of a different serotype in a subsequent infection, and cause a severe, potentially fatal form of the disease (Dengue haemorrhagic fever-Dengue shock syndrome). The present proposal seeks to further understanding of the role of the dengue RNA-dependent RNA polymerase NS5, which is essential for viral RNA replication, with ....Dengue virus is the causative agent of a mosquito-borne disease, Dengue fever, relevant to northern Queensland, where antibodies from a previous infection can complex with virus of a different serotype in a subsequent infection, and cause a severe, potentially fatal form of the disease (Dengue haemorrhagic fever-Dengue shock syndrome). The present proposal seeks to further understanding of the role of the dengue RNA-dependent RNA polymerase NS5, which is essential for viral RNA replication, within the viral infectious cycle. We intend to examine the subcellular targeting properties of a short central region (the interdomain) of NS5, which appears to play multiple roles in targeting to both the perinuclear Golgi-membranes and to the nucleus, as well as in inducing intracellular membranes derived from the Golgi which are the site of viral replication. We will determine how NS5 localisation-membrane induction may differ in insect and primate cells, and attempt to isolate binding partners of NS5 from the nucleus and Golgi compartment of insect and primate cells using various different approaches. Our studies should assist in understanding NS5's critical role in the Dengue infectious cycle, and contribute towards devising new anti-viral strategies such as vaccination and-or therapies targeted at the NS5 interdomain.Read moreRead less
A Functional Interaction Between Domains Of The Flavivirus NS5 Protein Presents A New Target For Antiviral Therapy
Funder
National Health and Medical Research Council
Funding Amount
$502,891.00
Summary
Mosquito-transmitted flaviviruses such as dengue, yellow fever, Japanese encephalitis and West Nile infect hundreds of millions of people and cause debilitating and fatal diseases. Developing anti-viral treatments against these diseases is a high priority. Our strategy is to develop small molecules that can bind to specific sites on viral proteins and prevent the virus from replicating and causing disease.
Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
Structural Characterisation Of Long Non-Coding RNA Bound Histone Modification Complexes
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Cancer is a disease associated with genetic and epigenetic changes of DNA. Epigenetics involves external changes to the DNA, switching processes “on” and “off”, to regulate gene expression. This project aims to provide powerful insight into key processes involved in epigenetic-based carcinogenesis, and thereby lay the foundation for producing novel cancer diagnostic markers and molecular based therapies.
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.