Molecular Characterisation Of Host Cell Targets Of Human Pathogenic Viruses And Evaluating Their Potential As Novel Therapeutic Targets.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed t ....There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed therapeutics against these deadly pathogens.Read moreRead less
Immune Therapies For Chronic Hepatitis B Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$359,085.00
Summary
Hepatitis B virus (HBV) causes acute and chronic infection leading to severe liver damage in many patients and increased risk of primary liver cancer. Worldwide ~350 million people have chronic HBV infection and, while a HBV vaccine is available that protects against new infections, current antiviral drug treatments for existing infection are largely ineffective. Thus, the aim of our project is to develop new treatments for chronic HBV infection using vaccination approaches. These therapies will ....Hepatitis B virus (HBV) causes acute and chronic infection leading to severe liver damage in many patients and increased risk of primary liver cancer. Worldwide ~350 million people have chronic HBV infection and, while a HBV vaccine is available that protects against new infections, current antiviral drug treatments for existing infection are largely ineffective. Thus, the aim of our project is to develop new treatments for chronic HBV infection using vaccination approaches. These therapies will be tested in ducks infected with the duck hepatitis B virus (DHBV), a model for human HBV infection. In brief, DHBV-infected ducks will be treated with a new antiviral drug, Entecavir (ETV) developed by Bristol-Myers Squibb, which blocks virus replication. To accelerate clearance of infected cells before drug-resistant viruses can emerge, the ducks will also be treated in combination with different novel therapeutic vaccines designed to induce strong humoral and cell mediated immune responses. Based on outcomes in initial experiments, we will adjust the vaccination protocol in ETV-treated ducks to maximize reductions in the levels of DHBV in liver and bloodstream, rates of death and clearance of DHBV-infected hepatocytes. Our ultimate goal is to define a protocol for combination antiviral and vaccination treatments that allows elimination of HBV infection, or that achieves a level of control of infection that eliminates ongoing disease by reducing virus loads to virtually undetectable levels.Read moreRead less
Molecular Characterization Of Dengue Virus Fusion And Antiviral Inhibitors.
Funder
National Health and Medical Research Council
Funding Amount
$573,557.00
Summary
Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries around the world, including Australia. Infection with dengue viruses cause severe and sometimes fatal disease. This proposal focuses on the way dengue virus enters cells and the development of drugs that will prevent virus entry. We have already identified compounds that inhibit the entry process of dengue into cells and this project will significantly build on these early findings.
The Role Of Endocannabinoids In Chronic Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$563,002.00
Summary
Hormones related to cannabis help to regulate fat stores in the human body. CB1 antagonists are a new class of drugs that block these hormones and are being tested for the treatment of obesity and fatty liver. We discovered that Hepatitis C makes the liver more sensitive to these hormones, helping the hepatitis C virus to replicate. This project will determine the mechanisms by which CB1 antagonists prevent hepatitis C virus replication and their potential as a novel therapy for this disease.
Systematically Exploring The Contribution Of Immunoproteasome To Immunodominance And T Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$499,860.00
Summary
Vaccine will help us to fight both infectious diseases and malignancy. However, there are few successful vaccines for infectious agents and there is simply no vaccine to cure any tumor at the moment. So, it is essential for us to learn the basics related to vaccine development. Killer T cells eliminate tumour cells or virally infected host cells by recognising fragments (epitopes) derived from tumour- or virus-derived proteins displayed on a host molecule called MHC. Normally multiple epitopes a ....Vaccine will help us to fight both infectious diseases and malignancy. However, there are few successful vaccines for infectious agents and there is simply no vaccine to cure any tumor at the moment. So, it is essential for us to learn the basics related to vaccine development. Killer T cells eliminate tumour cells or virally infected host cells by recognising fragments (epitopes) derived from tumour- or virus-derived proteins displayed on a host molecule called MHC. Normally multiple epitopes are generated as part of the protein recycling program referred as proteine degradation which is mainly conducted by bundled enzyme complex, called proteasome. Two major forms of proteasomes are expressed by most cells. One called house-keeping proteasome and the other, which replaces the house-keeping one during viral infections is called immunoproteasome. The role that the immunoproteasome plays during anti-viral and anti-tumoral immune responses is not fully understood. In addition, the immunoproteasome is also expressed by a few cell types that do not suppose to need it if its function is entirely to generate better epitopes for MHC to display. In this project, we will sytematically explore the contribution of the immunoproteasome to overall anti-viral and anti-tumoral immune responses in three mouse model systems. The shared feature of these systems is that multiple killer T cell epitopes have been defined, which could potentially provide us with very sensitive assessments. The three systems are anti-influenza, anti-vaccinia virus and anti-tumor antigen (NY-ESO-1) mouse models.Read moreRead less
The Role Of Actin-based Motility As A Virulence Mechanism And Potential As An Antiviral Target
Funder
National Health and Medical Research Council
Funding Amount
$325,798.00
Summary
Our repertoire of effective treatments for infectious diseases is fast becoming exhausted as resistance to antibiotics and antivirals evolves and rapidly spreads throughout our community. We have developed a new paradigm in treating viral diseases that we predict will not give rise to resistance, and this project will be the first to demonstrate the effectiveness of this novel therapy in an endemic disease model.
Improved Treatment Of Congenital Cytomegalovirus Disease Through Study Of Placental Models Of Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$674,918.00
Summary
Congenital CMV is the second most common cause of fetal malformation in Australia, and yet most pregnant mothers do not know about it, nor how to prevent congenital CMV in their baby. It is a viral infection that can severely damage the unborn baby. Our research aims to find more about how the virus damages the baby, and whether antiviral drugs are useful in reducing infection of the baby, and also reducing damage to the baby from such infection. If successful, these studies will be the basis fo ....Congenital CMV is the second most common cause of fetal malformation in Australia, and yet most pregnant mothers do not know about it, nor how to prevent congenital CMV in their baby. It is a viral infection that can severely damage the unborn baby. Our research aims to find more about how the virus damages the baby, and whether antiviral drugs are useful in reducing infection of the baby, and also reducing damage to the baby from such infection. If successful, these studies will be the basis for clinical trials in pregnant women.Read moreRead less
Hepatitis C affects a quarter of a million Australians, causing insidious but progressive liver disease which culminates in liver failure or cancer. There is no vaccine and prevention programs have limited effectiveness, but new antiviral therapies now offer high rates of cure. This Program will evaluate strategies to improve the health of those affected and prevent new infections by better understanding of the virus and the body’s immune response, including scarring and liver cancer formation.
Ensuring Local Capability In Complex Systems Methodology To Inform Infectious Disease Policy
Funder
National Health and Medical Research Council
Funding Amount
$464,847.00
Summary
Influenza is an example of an infectious disease that remains a global challenge, causing annual outbreaks and disruptive pandemics. My group works with basic scientists and social researchers to understand the way influenza and other infections spread, and how drugs and vaccines protect. I have built local capability in computer simulation modeling that brings this rich body of evidence together, to promote understanding of disease and inform health policy in Australia and internationally.