Understanding The Role Of Ongoing Viral Activity In Herpes Simplex Virus Latency
Funder
National Health and Medical Research Council
Funding Amount
$980,762.00
Summary
The virus that causes cold sores and genital herpes has a dormant phase from which renewed infection can recur. We recently discovered that this dormant phase is more active than we thought and we now want to learn how the body acts to suppress the virus so that these defence mechanisms might be improved to stop recurrent infections.
Chikungunya Virus Disease; The Role Of Proteases And Their Receptors
Funder
National Health and Medical Research Council
Funding Amount
$682,716.00
Summary
Chikungunya virus (CHIKV) is a mosquito borne virus related to the Australian Ross River virus. The arthritic disease caused by these viruses is often poorly managed by current treatments. We have recently identified several proteins call proteases that circulate in the blood of infected people and promote arthritis. If successful the grant will provide new treatment options for these (and perhaps other) diseases using recently developed drugs that inhibit the activity of these proteases.
The Role Of The Interaction Of The CMV M11 Immune Evasion Molecule With CD44 In Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$457,500.00
Summary
Herpesviruses can cause infections that persist for the lifetime of the host. They have evolved many mechanisms to elude the host's immune response that would otherwise eliminate them. One memberof the herpesvirus family that is particularly adept at avoiding host immunity is cytomegalovirus. This virus, while not causing symptoms in healthy individuals, is a significant cause of disease and mortality in individuals with suppressed immune systems such as transplant and AIDS patients, and in the ....Herpesviruses can cause infections that persist for the lifetime of the host. They have evolved many mechanisms to elude the host's immune response that would otherwise eliminate them. One memberof the herpesvirus family that is particularly adept at avoiding host immunity is cytomegalovirus. This virus, while not causing symptoms in healthy individuals, is a significant cause of disease and mortality in individuals with suppressed immune systems such as transplant and AIDS patients, and in the fetus which has a poorly developed immune system. In the current project we will explore at a molecular level how a virus-encoded molecule called m11 interferes with the functions of a cellular receptor called CD44 that has a range of cell functions including cell migration, activation and proliferation and signal transduction. The interaction of m11 with CD44 modifies cell migration and is likely to affect cell activation. Defining how m11 mediates its affects will allow us to define strategies to develop potential antiviral therapies. As CD44 is also involed in contributing to a range of diseases where inappropriate inflammation develops it may be that m11, or derivatives of it, could be harnessed to ameliorate these inflammatory diseases.Read moreRead less
Understanding How Virus Infection Accelerates Type 1 Diabetes Development
Funder
National Health and Medical Research Council
Funding Amount
$610,774.00
Summary
We linked rotavirus infection in children at-risk of type 1 diabetes with faster diabetes development. A heightened response to the virus is implicated by our mouse model studies. We will determine if more rapid mouse diabetes due to rotavirus requires this heightened response, and if this response is also made by cells from diabetes patients after stimulation with rotavirus or other relevant viruses. These studies are vital to learn how viruses affect type 1 diabetes and devise interventions.
Elucidating The Pathogenic Role Of Rotavirus Infection In Type 1 Diabetes Development
Funder
National Health and Medical Research Council
Funding Amount
$535,579.00
Summary
Rotavirus infection is the main cause of severe diarrhoea in children, and has been implicated in accelerated progression of genetically at-risk children towards type 1 diabetes in two independent studies. My group has further discovered that rotavirus also accelerates diabetes onset in mice in a novel immunological process. In this project, we will determine the mechanism behind this disease exacerbation in the mice, to facilitate understanding of the process in children.
Exploration Of The Role Of Microbes In Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$687,974.00
Summary
This fellowship will investigate diseases of the gastrointestinal tract of children. The research program will undertake a range of is a highly innovative projects including; development of an effective rotavirus vaccine to be administered to newborns; genetic characterisation of rotavirus strains able to escape vaccine protection; and how alterations in the human gut microbiome (bacteria and viruses) influence the development/relapse of CrohnÍs disease.
Molecular Mechanism And Therapeutic Implications Of Prion Disease Strain Types In Sporadic Creutzfeldt Jakob Disease.
Funder
National Health and Medical Research Council
Funding Amount
$345,634.00
Summary
The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an ....The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms also exist. Prion diseases are transmissible by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been conclusively identified. However, a major component of purified prions is an abnormal disease associated form of the host prion protein. Differences in the duration of illness and pathology of sporadic CJD suggests that the disease may be caused by different prion strains. The existence of different prion strains may explain the limited clinical success of anti-prion therapeutics modeled in rodent models of prion diseases. In this study a cell-free model of prion propagation will be used to investigate the basis of human prion strains. This assay will also be used to identify and determine whether the therapeutic efficacy of anti-prion compounds is influenced by human prion strain type. This study will represent the first host species and prion strain specific screen of anti-prion therapeutics aimed at developing the best possible model for the identification and development of therapeutics for human prion diseases.Read moreRead less
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$827,660.00
Summary
Infections with mosquito-borne viruses are increasing at an alarming rate worldwide. Ross River virus is endemic in parts of Australia, PNG and Pacific islands, while chikungunya virus is distributed globally and causes recurrent pandemics that involve millions of people. These viruses cause severe musculoskeletal disease for several months after infection. This project aims to establish how these viruses interact with the human host to cause disease and may provide a basis for new treatments.