Combination Antiviral And Immune Therapies For Hepatitis B Virus Infection.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Hepatitis B virus (HBV) causes acute and persistent (chronic) infection with varying degrees of liver damage and a strong association with the development of liver cancer. Worldwide ~ 250 million people have persistent HBV infection and while a HBV vaccine is available that protects against infection, current treatments for existing infection are largely ineffective. We wish to study a combination of antiviral drug therapy and vaccination with DNA vaccines, to develop new treatment protocols for ....Hepatitis B virus (HBV) causes acute and persistent (chronic) infection with varying degrees of liver damage and a strong association with the development of liver cancer. Worldwide ~ 250 million people have persistent HBV infection and while a HBV vaccine is available that protects against infection, current treatments for existing infection are largely ineffective. We wish to study a combination of antiviral drug therapy and vaccination with DNA vaccines, to develop new treatment protocols for persistent hepatitis B virus (HBV) infection. The human HBV is a member of the hepadnavirus family that includes a number of other very similar host-specific viruses. Therapies will be tested in ducks infected with the duck hepatitis B virus (DHBV) as these animals provide the only model system available in Australia for development of HBV therapies. DHBV-infected ducks will be treated with a new and extremely potent antiviral drug Entacavir (ETV; Bristol-Myers Squibb). Drug treatment will be combined with various DNA vaccination protocols, including new strategies that involve DNA vaccine priming and recombinant fowlpoxvirus (rFPV) boosting of immune responses. Inoculation of DNA vaccines and rFPV results in expression of viral proteins that are presented to the immune system and evoke strong immune responses. 'Prime boost' protocols with DNA vaccines and rFPV have shown promise for protection against and treatment of human immunodeficiency virus (AIDS virus) infection. We will assess the effect of treatment by measuring levels of DHBV in liver and blood, clearance of infected cells and serological changes. The ultimate aim is to develop successful therapies that can then be applied to treatment and elimination of HBV infection in humans.Read moreRead less
Title: Structure of hepadnaviral pre-genomic RNA. We aim to study the replication strategy of human hepatitis B virus (HBV), a member of the hepadnavirus family. Hepadnaviruses infect hepatocytes in the liver and are released in high numbers into the bloodstream. Infection is transmitted by blood or sexual contact. Hepadnaviruses cause acute and chronic infection with varying degrees of liver disease. The HBV DNA genome is formed by copying of a viral pre-genome made of RNA, into DNA. This proce ....Title: Structure of hepadnaviral pre-genomic RNA. We aim to study the replication strategy of human hepatitis B virus (HBV), a member of the hepadnavirus family. Hepadnaviruses infect hepatocytes in the liver and are released in high numbers into the bloodstream. Infection is transmitted by blood or sexual contact. Hepadnaviruses cause acute and chronic infection with varying degrees of liver disease. The HBV DNA genome is formed by copying of a viral pre-genome made of RNA, into DNA. This process is called reverse transcription and is performed by the viral polymerase. Reverse transcription occurs within viral nucleocapsids made of core antigen. After formation of the new viral DNA genome, nucleocapsids are enveloped in surface antigen and are released from the cell. It is assumed that 1 copy of HBV pre-genomic RNA is packaged within each viral nucleocapsid. However, members of the retrovirus family that have common evolutionary origins to hepadnaviruses and also replicate via reverse transcription, contain 2 copies of RNA. The human immunodeficiency virus (HIV), the AIDS virus, is a well-studied example. In HIV infection 2 RNA genomes are packaged into each nucleocapsid and form a dimeric RNA genome. The HIV RNA is able to fold into a series of stem loops that promote formation of dimers. During the reverse transcription step in HIV replication, the polymerase switches templates and forms new combined strains of virus. The project aims to determine if 2 copies of pre-genomic RNA are packaged into HBV nucleocapsids. HBV pre-genomic RNA is able to form stem loop structures similar to those in HIV and has the potential to form dimeric RNA. If 2 copies of HBV pre-genomic RNA are packaged this will allow us to redefine the viral replication strategy and to develop a greater understanding of the relationships between hepadnaviruses and retroviruses. The formation of dimers will also provide a mechanism for recombination between HBV strains.Read moreRead less
I am a molecular parasitologist exploring parasitism in blood-feeding human helminths, with a particular focus on the molecular biology of parasite feeding and immune evasion. I am utilizing this information to develop anti-helminth recombinant vaccines a
Next Generation Of Medical Devices And Diagnostics
Funder
National Health and Medical Research Council
Funding Amount
$2,738,220.00
Summary
This Investigator Project will deliver innovative technologies that improve patient wellbeing, make significant economic impact and contribute to answering complex biological questions. This will happen via delivering breakthrough technologies to prevent infections and diagnose diseases – two area that currently require substantial technological advances. In addition to helping patients and clinicians, the project will also deliver solid body of new knowledge that is currently missing.
Clinical Impact Of Clonal Pseudomonas Aeruginosa In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$547,238.00
Summary
In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on ....In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on the major bacterial problem, Pseudomonas aeruginosa. Several studies from Australia and the UK, including our own have shown that about 30% to 45% of patients share the same strain of Pseudomonas aeruginosa within a centre. We know that two dominant strains of Pseudomonas aeruginosa are found in CF centres on the eastern board of Australia. This is unexpected as this bacterium is usually acquired from the environment. The emergence of these clonal strains is causing increasing anxiety in the CF community. This study is designed to provide vitally needed information on the clinical implications of being infected by an clonal strain of Pseudomonas aeruginosa and the risk factors for the acquisition of an clonal strain. This new information will provide a rationale basis for the need for changes to infection control policies (including patient segregation), better outcome predictors for patients infected with clonal strain of Pseudomonas aeruginosa.Read moreRead less
Treatment Of Cerebral Palsy - An Experimental Approach
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Cerebral palsy is characterised by disordered movement evident early in life leading to lifelong disability. The motor disorder arises from an abnormality within the white-matter of the brain that is non-progressive and is identifiable soon after birth. In humans and experimental models of fetal infection there is an increase in markers of inflammation. We will use induce ovine fetal infection and white matter injury to examine if anti-inflammatory treatments can prevent fetal brain damage.
Mechanisms Regulating Establishment Of Persistent Herpesvirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$511,446.00
Summary
Herpesviruses are a major cause of disease worldwide and are amongst the most successful human pathogens, with some viruses infecting more than 80% of the world's population. This group of viruses persist and reactivate in hosts and induce immunosuppression.The control of herpesviruses infections thus represents an important clinical goal. Understanding the mechanisms involved in the induction of viral persistence and immunosuppression is a crucial step towards developing better therapies.
Determinants Of Cytomegalovirus Salivary Gland Persistence
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Human cytomegalovirus (HCMV) persists for extended periods in the salivary gland, an organ of viral transmission. It is not clear how the virus avoids immune mediated control in this tissue. This aspect of viral pathology will be assessed in a mouse model using two strains of murine CMV which exhibit marked differences in salivary gland persistence. The role of tissue tropism (inhibition of apoptosis), viral immune evasion and host immunity in salivary gland persistence will be studied.
Cluster Randomised Trial Comparing One Versus Two Doses Of Ivermectin For Mass Drug Administration To Control Scabies
Funder
National Health and Medical Research Council
Funding Amount
$540,512.00
Summary
Scabies is a common skin disease in developing countries, in particular in the Pacific region. In the Western Province of Solomon Islands, one in two children suffer from the infestation, and 20% of the population. We know that mass drug administration with two doses of oral ivermectin is effective to reduce the burden of scabies in the community. We now propose a study to determine whether one single dose is as effective. This would have major public health benefits.
Novel Octapeptin Antibiotics Targeting Extremely Drug Resistant 'superbugs'
Funder
National Health and Medical Research Council
Funding Amount
$946,024.00
Summary
The World Health Organization (WHO) has identified antimicrobial resistance as one of the three greatest threats to human health. Many clinicians worldwide have already been confronted with the reality of infections caused by extremely drug resistant (XDR) bacterial 'superbugs' resistant to all available antibiotics. This project aims to develop safe and efficacious octapeptin antibiotics for the treatment of life-threatening infections caused by problematic XDR ‘superbugs'.