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Defining The Requirement For The Inhibition Of Bak To The Pathogenesis Of Cytomegalovirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
Apoptosis, or programmed cell death is a powerful defence mechanism against viral infection. Thus, to replicate efficiently viruses have evolved means to inhibit apoptosis. The central aim of this work is to understand how cytomegalovirus prevents cell death protein during infection. The proposed studies will improve our understanding of the mechanisms that regulate viral replication and will contribute insights into the normal processes that control cell survival.
Progression Of Influenza Virus Within The Respiratory Tract
Funder
National Health and Medical Research Council
Funding Amount
$513,716.00
Summary
We are exploring how influenza virus moves down the respiratory tract after infecting the nose. We have identified a component of mouse saliva that can halt the progression from the nose to the trachea and lungs and will determine how it binds to the virus to stop infection. We will also examine how human and highly lethal avian viruses move from the upper respiratory tract to other organs in the mouse and also in the ferret, which is a much better model for mimicking what happens in man.
The West Nile Viral Protease, NS3: A Target For Antiviral Drug And Vaccine Design
Funder
National Health and Medical Research Council
Funding Amount
$230,500.00
Summary
The West Nile Virus (WNV) was first isolated from a woman in the West Nile region of Uganda in 1937. It is one of ~70 known flaviviruses (e.g. Dengue fever, Yellow fever, West Nile, Kunjun, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis, Australian encephalitis and the related hepatitis C virus) which annually infect hundreds of millions of people worldwide, particularly in tropical and sub-tropical areas, and cause major public health problems. WNV is endemic in the Midd ....The West Nile Virus (WNV) was first isolated from a woman in the West Nile region of Uganda in 1937. It is one of ~70 known flaviviruses (e.g. Dengue fever, Yellow fever, West Nile, Kunjun, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis, Australian encephalitis and the related hepatitis C virus) which annually infect hundreds of millions of people worldwide, particularly in tropical and sub-tropical areas, and cause major public health problems. WNV is endemic in the Middle East, parts of Africa and Europe, but recent epidemics in Israel (1998), Romania (1996), United States (1999), and UK (2003) have been characterized by severe symptoms , severe neurological pathology, and fatalities. In the USA alone there were 4,156 infections and 284 deaths in 2002, 9122 infections and 223 deaths in 2003, and this mosquito borne virus has quickly spread since 1999 through all USA states and into Canada and Mexico (http:--www.cdc.gov-ncidod-dvbid-westnile-index.htm). No treatments or vaccines are available. This project focuses on an enzyme, known as the West Nile Virus NS3 protease, that is essential for replication of the virus. By studying the enzyme in the laboratory we can design small molecules that can block its function and these have real potential as leads for development of drug treatments for people infected by this virus. A precedent is the success of inhibitors of HIV-1 protease that are the most effective treatment for humans with HIV-infections. Our studies will also be used to develop potential vaccines. The science involves experts on protease enzymes, drug design and development, virology including West Nile virology, and vaccine development. We expect to generate drug and vaccine candidates and new information for their development that is at the cutting edge of West Nile Virus research.Read moreRead less
Nuclear Transport In Health And Disease; Towards Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
This research fellowship will enable new therapeutic approaches to viral disease and cancer that target the transport process. I have already licenced an inhibitory molecule for Dengue virus which is progressing towards the clinic. I will now extend my research into a vibrant translational program of developing anti-viral (HIV, Respiratory Syncytical Virus, VEEV) as well as anti-cancer agents that will represent realistic therapeutic options in the near future.
Understanding The Role Of The Scaffolding Protein D13 In Poxvirus Assembly And Its Inhibition By Rifampicin
Funder
National Health and Medical Research Council
Funding Amount
$371,275.00
Summary
Smallpox is one the most notorious diseases in human history. Despite its eradication in the 1970s, human cases of animal poxviruses such as monkeypox virus and the potential use of smallpox as a bioterrorism weapon have called for an improved preparedness of Australia against (re)-emerging poxviruses. This project combines structural biology approaches to understand the complex assembly of poxviruses and provide the basis for the development of broad-spectrum antiviral drugs.
Identifying Novel Regulators Of RNA Receptor Signalling To Modulate Viral Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$312,034.00
Summary
Viruses elicit a rapid immune response upon infection that is crucial for controlling viral spread and disease. Human cells detect viral molecules to coordinate the the production of anti-viral proteins. The aim of this research is to identify new genes that are essential for controlling the initial immune response to viral infection. This research will help us understand how virus infection can be controlled appropriately, and may lead to the development of new anti-viral therapeutics.
Towards A New Class Of Reverse Transcriptase Inhibitor For HIV Prevention
Funder
National Health and Medical Research Council
Funding Amount
$688,833.00
Summary
There remains an urgent need for new HIV prevention strategies. New HIV drugs that block the virus by distinct ways are needed to prevent transmission of drug resistant HIV. This study seeks to identify very small molecules called “fragments” that bind to previously undiscovered pockets on the HIV reverse transcriptase to stop its function, and that can be used as building blocks to design more potent HIV drugs to be used solely for HIV prevention.
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
Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
Interaction Of Anti-viral IDO And NOS2 In Vivo In A Novel Murine STD Model.
Funder
National Health and Medical Research Council
Funding Amount
$573,629.00
Summary
Sexually transmitted viral diseases (STD) are increasing globally, but we know little of how virus is controlled early in infection. We have shown for the first time in vivo, in our STD model, that during an antiviral immune response, soluble factors turn on an enzyme, indoleamine 2,3-dioxygenase (IDO), to break down and deplete the amino acid, L-tryptophan, starving virus to reduce growth early in STDs. Our project will further define the action and control of IDO in STD.