The Molecular Processes Involved In Age-related Human Nuclear Cataract
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
This project seeks to understand the molecular basis for age-related nuclear cataract, and in particular the role of our UV filter compounds. By gaining an understanding of the mechanism of cataract we hope to be able to develop ways to interfere with the process and thus prevent, or at least delay, human cataract. Experiments will be undertaken to determine the extent of covalent binding of the most reactive UV filter, 3-hydroxykynurenine, to lens proteins (crystallins) isolated from normal hum ....This project seeks to understand the molecular basis for age-related nuclear cataract, and in particular the role of our UV filter compounds. By gaining an understanding of the mechanism of cataract we hope to be able to develop ways to interfere with the process and thus prevent, or at least delay, human cataract. Experiments will be undertaken to determine the extent of covalent binding of the most reactive UV filter, 3-hydroxykynurenine, to lens proteins (crystallins) isolated from normal human lenses of various ages, and from cataract lenses. In addition, the properties of lens crystallins that have been modified in model systems by kynurenine, 3-hydroxykynurenine and 3-hydroxykynurenine glucoside will be investigated. This will include examination of the impact of the UV filter modifications on the formation of protein radicals following exposure of the crystallins to UV light and an investigation of the hypothesis that the protein-bound UV filters act as sites for both complexing of metals and their chemical reduction. Oxidation is known to be involved in cataract and experiments will also be undertaken to measure the concentration of oxygen in the lens nucleus, so that the model studies more accurately reflect conditions within the lens, and to see if the levels of oxygen may inflluence the onset of cataract.Read moreRead less
Remodelling Of Bacterial Outer Membranes: Implications For Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
We have identified proteins located in bacteria that are responsible for growth and the transport of essential nutrients. We will use a combination of bacterial genetics, protein biochemistry and immunological techniques to fully characterize these proteins. This strategic knowledge has direct implications for vaccine development and National security, since similar species of bacteria were amongst the first biological weapons.
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
A Temporal Profile Of Signaling Via Phosphorylation During Myocardial Ischemia - Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$369,641.00
Summary
Cardiovascular disease (CVD) is the major cause of death in Australians and sequelae post-myocardial ischemia - reperfusion (I-R) are responsible for the greatest proportion of CVD-related mortality. Despite this burden, there is little known of the molecular events that mediate I-R. This project will utilize cutting-edge technology to elucidate the molecular signaling events that lead to I-R injury, as well as determine the basis for protection afforded by clinical pre- and post-conditioning.
Role Of Sirtuins In The Regulation Of The Carcinogen Metabolising Arylamine N-acetyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$327,324.00
Summary
This project will investigate critical biochemical pathways that regulate metabolic differences in normal and cancer cells. By understanding how these processes differ, novel approaches for detecting and managing cancer cell proliferation in humans may be achievable.
I am interested in determining the molecular basis of immune recognition of foreign and self-antigens in the context of viral, tumor and auto-immunity as well as transplantation. In addition to fundamental observations this knowledge is also applied in va
Characterising Protein And Membrane Changes In Age-related Cataract Lenses.
Funder
National Health and Medical Research Council
Funding Amount
$441,624.00
Summary
Cataract is the major cause of blindness worldwide. At present the only treatment for cataract, is surgery. This, however, is associated with complications (e.g. posterior capsule opacification), is expensive (a major component of the Health budget) and cannot keep pace with the incidence of cataract in developing nations. In addition, due to the greying of the community , this problem will be of increasing importance in the future. For prevention, we need to understand why cataract develops.