Targeting To Mitochondria Of Tail-Anchored Proteins. Defining The Molecular Apparatus Of Targeting.
Funder
National Health and Medical Research Council
Funding Amount
$254,751.00
Summary
The cells of the body have an intricate and dynamic internal architecture, with the components (proteins, lipids, and nucleic acids) of the cell carefully arranged. It is widely viewed that just how each component finds its place in the cell, the cellular adressing system, is of critical importance. This was recognized this year by the award of the Nobel Prize in Medicine to Dr. Gunter Blobel for his work on the signals that direct different proteins to their correct destination. One such destin ....The cells of the body have an intricate and dynamic internal architecture, with the components (proteins, lipids, and nucleic acids) of the cell carefully arranged. It is widely viewed that just how each component finds its place in the cell, the cellular adressing system, is of critical importance. This was recognized this year by the award of the Nobel Prize in Medicine to Dr. Gunter Blobel for his work on the signals that direct different proteins to their correct destination. One such destination is the mitochnondria, the particles in the cell that produce chemical energy. The work in this proposal is designed to define precisely the molecular apparatus that targets a group of proteins to mitochondria. This group, proteins that are inserted into the mitochondria at one end of the protein, includes a variety of critical proteins, including those that determine the life or death of a cell. We will define both the address contained within those proteins, and the machinery on the mitochondria that recognizes that address, and ensures that those proteins will become part of the mitochondria. This research has two applications. By understanding the address, we will be able to decode the vast amount genomic data that is being produced, to predict exactly which proteins are delivered to mitochondria. Secondly, by understanding the targeting machinery, we may begin to design molecules that can inhibit its function, and thus manipulate the delivery of those proteins that affect cell life and death.Read moreRead less
GPI Anchored Forms Of The Dengue Virus NS1 Protein: Production And Role In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$203,448.00
Summary
Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we h ....Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we have identified. We plan to study the role that this protein plays in the more severe and often fatal forms of dengue infection (dengue haemorrhagic fever and dengue shock syndrome). In these more severe and life threatening forms of dengue the blood vessels of these patients become leaky. It is thought that this is caused by the secretion of certain chemicals (cytokines) from infected cells. We have shown that dengue infected human cells, which have the unusual form of NS1 protein on their surface, are capable of being activated by antibodies. Antibodies are proteins which are produced by the human body to fight infection. We aim to study whether cytokines are secreted from infected human blood cells activated in this way and whether these cytokines cause blood vessels to become leaky. We will also study how the virus produces this variant form of NS1 in the two host species that the virus infects; mosquito and human. These studies will increase our understanding of dengue virus infection and will provide valuable information concerning the role that this unusual form of the degue virus protein NS1 plays in the severe forms of dengue fever; dengue haemorrhagic fever and dengue shock syndrome.Read moreRead less