Regulation Of Endosome Function By The AAA-ATPase Vps4
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Cells respond to many signals from the environment. Some signals tell cells to grow and divide and other signals tell cells to rest. These signals are usually in balance in healthy cells. To prevent cells from growing and dividing in an uncontrolled manner and forming a cancer, there are mechanisms to turn off signals for growth. One mechanism is to destroy the proteins responsible for growth signalling. This involves flipping (by a process called multivesicular body, or MVB, sorting) the signal ....Cells respond to many signals from the environment. Some signals tell cells to grow and divide and other signals tell cells to rest. These signals are usually in balance in healthy cells. To prevent cells from growing and dividing in an uncontrolled manner and forming a cancer, there are mechanisms to turn off signals for growth. One mechanism is to destroy the proteins responsible for growth signalling. This involves flipping (by a process called multivesicular body, or MVB, sorting) the signalling protein from one side of the membrane where signalling occurs to the other side where signalling cannot occur and where the signalling protein can be degraded. Interestingly, it has recently been discovered that some viruses (including the AIDS virus) use the same MVB sorting mechanisms to escape from infected cells. Instead of undergoing MVB sorting into an internal compartment and getting degraded, however, the virus is able to use the same mechanism to flip out of the cell. How MVB sorting occurs is not known, but the mechanism has been conserved through evolution and even microbes like yeast can perform MVB sorting of proteins. We are investigating a component of the MVB sorting mechanism known as Vps4 which is present in both human cells and in yeast cells. Since the human Vps4 and yeast Vps4 seem to function in the same way, and since powerful molecular genetic approaches can be used in yeast to elucidate how proteins function (some of which are not possible with human cells), we are using yeast to investigate Vps4 function. Once we understand how the yeast Vps4 works, we will be able to test if human Vps4 works the same way. Understanding the MVB sorting mechanism will give us information on how cells prevent uncontrolled growth and division and may also help us find ways of preventing AIDS infection.Read moreRead less
Resolving Human Immunodeficiency Virus (HIV) Transmission
Funder
National Health and Medical Research Council
Funding Amount
$745,213.00
Summary
To increase the breadth of HIV prevention strategies, it is imperative that we biologically understand how HIV enters our bodies. Through two unique clinical cohorts, we will determine why circumcision is protective and how a commonly acquired sexual transmitted infection (human papilloma virus) can increase HIV transmission.
Intrinsic Host Antiviral Activity Against Pathogenic Filoviruses
Funder
National Health and Medical Research Council
Funding Amount
$488,754.00
Summary
Bats are a major reservoir for deadly human viruses including Ebola and Marburg virus. In contrast to humans, bats can be infected with these viruses without showing clinical signs of disease. The reason why bats can co-exist with these viruses is unknown. This study will determine if a bat antiviral molecule contributes to limiting virus release compared to the human version that could reveal strategies to prevent and control these deadly viruses in humans.
Identification Of Host Factors That Restrict Influenza Virus Replication In Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$566,446.00
Summary
Influenza virus infects different cells in the airways, including immune cells (macrophages) and non-immune cells (epithelial cells). Epithelial cell infection results in virus amplification and release whereas macrophage infection leads to virus destruction. This project will identify cellular factors expressed by macrophages that block virus amplification and release. Identification of novel antiviral factors is an important step towards developing strategies to reduce influenza disease.
Identification Of Host Restriction Factors That Block Respiratory Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$956,898.00
Summary
Following inhalation, respiratory viruses can infect and grow in airway epithelial cells. Although immune cells such as macrophages are also susceptible to infection, this is generally abortive and new viruses are not released. This project will identify proteins induced in macrophages that block respiratory viruses and prevent their spread in the airways. We will also define mechanisms by which some virulent strains overcome this block to grow in macrophages.
The Role Of Varicella Zoster Virus In Modulating Cutaneous Infection
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
Varicella zoster virus (VZV) causes two skin diseases: chickenpox and shingles. VZV can causes significant morbidity in children and adults and life-threatening disease in immunocompromised people. This project aims to improve our understanding of how VZV affects the function of specialised skin cells to provide information for the development of a better vaccine to lessen the impact of VZV disease on the community.
Pandemic Influenza Vaccine: Exploiting The Conserved HA Cleavage Site
Funder
National Health and Medical Research Council
Funding Amount
$243,300.00
Summary
Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preve ....Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preventing the viral spike protein from being cleaved and remain immature. This idea is particularly suited to fight the bird flu, as all pathogenic bird influenza viruses cleave HA spike proteins within the infected cell.Read moreRead less