Structural Investigation Into The Regulation Of The Colony Stimulating Factor Receptor, C-FMS.
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
The colony stimulating factor receptor, c-FMS is a member of a family of protein signalling molecules expressed on the cell surface that are implicated in the development of serious diseases in humans, such as inflammatory diseases and cancer. A number of important proteins bind to and regulate c-FMS in different ways. I intend to visualise these interactions to further understand how c-FMS activity is controlled by alternative means.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
I am a protein crystallographer determining the structures of medically important proteins such as proteases. I am also a bioinformatician leading the development of informatics systems for automated highthroughput crystallography, and bioinformatic analy
Post-translational Control Of Indoleamine 2,3-dioxygenase
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
It is apparent that a protein called indoleamine 2,3-dioxygenase is important for controlling the immune system of relevance to various normal and disease conditions including pregnancy, cancer, inflammation, infectious disease and autoimmunity. Despite this little is known about how this important protein is controlled. The aim of this project is to better understand how this protein is regulated that can highlight ways in which to alter the enzymes activity to modulate immune responces.
Biochemical Reconstitution Of The Ubiquitin Ligase Pathway Defective In Fanconi Anaemia
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Fanconi Anemia (FA) is characterised by loss of vital blood cells but also 700x risk of developing leukaemia and other cancers. FA is caused by an inherited defect in one of 15 different genes that provide a signal and repair mechanism protecting cells from cancer causing mutations. By reconstructing this signaling mechanism in the test tube we will determine how it contributes to cancer protection, and highlight potential strategies for treatment of FA and leukaemia in the general population.
The Molecular Mechanism Of Sphingosine Kinase Activation
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Many cell processes like growth, death and differentiation are controlled by hormones and other molecules that interact with receptors on the outside of the cell. When this type of molecule binds to a receptor, it often triggers the production of signaling molecules inside the cell that initiate a change in the cells behaviour. The lipid molecule, sphingosine phosphate has been identified as such a signaling molecule that appears to be involved in the regulation of a diverse array of important m ....Many cell processes like growth, death and differentiation are controlled by hormones and other molecules that interact with receptors on the outside of the cell. When this type of molecule binds to a receptor, it often triggers the production of signaling molecules inside the cell that initiate a change in the cells behaviour. The lipid molecule, sphingosine phosphate has been identified as such a signaling molecule that appears to be involved in the regulation of a diverse array of important mammalian cellular processes. Recent studies have found that sphingosine phosphate is involved in the inflammation of cells, and if its production can be blocked, inflammation is not seen. Therefore, this provides a potential target for therapeutic intervention in the inflammation process. However, the manner by which cells regulate sphingosine phosphate levels is not well known. It is known that sphingosine phosphate is produced by the enzyme sphingosine kinase, and strong evidence suggests that changes in this enzyme's activity in the cell regulate sphingosine phosphate levels. However, how the cell changes the levels of sphingosine kinase activity is completely unknown. This study will investigate this problem with the view that understanding this process will allow the development of new drugs to block increases in sphingosine kinase activity, preventing increases in sphingosine phosphate levels, and it turn, preventing cellular inflammation.Read moreRead less
Biochemical Analysis Of Akt 3-specific Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$349,375.00
Summary
The Akt family of enzymes consists of 3 protein kinases (Akt 1,2 and 3) and has been shown to regulate many normal cellular processes such as cell proliferation, growth, survival and motility, as well as the growth of new blood vessels. All these processes are critical for cancers to grow. However, few studies have distinguished the roles of the individual family members. Our preliminary data revealed Akt3 is far more active than the other two forms. Furthermore, using our unique Akt3 specific a ....The Akt family of enzymes consists of 3 protein kinases (Akt 1,2 and 3) and has been shown to regulate many normal cellular processes such as cell proliferation, growth, survival and motility, as well as the growth of new blood vessels. All these processes are critical for cancers to grow. However, few studies have distinguished the roles of the individual family members. Our preliminary data revealed Akt3 is far more active than the other two forms. Furthermore, using our unique Akt3 specific antibody, we find Akt 3 protein and activity levels are high in rapidly proliferating ovarian cancer cell lines and in primary ovarian tumours. The aim of this proposal is to characterise the mode and role of signalling via Akt3, including the identification of targeted substrates and signaling pathways and the outcomes of Akt3 driven signaling on cellular properties. These studies will provide important clues to understanding how this family member functions in both health and disease. Elucidation of the basis of Akt3 dependent signalling will open the possibility for the development of drugs that interfere with Akt3 function (for example in high Akt 3 expressing tumours like those of the ovary). In the long term, extension of our profiling studies to other tumour types will give a novel insight into the extent of Akt3 de-regulation as a key mediator of cancer formation.Read moreRead less
Redox Control Of The Immune Regulatory Protein, Indoleamine 2,3-dioxygenase
Funder
National Health and Medical Research Council
Funding Amount
$576,538.00
Summary
An enzyme called indoleamine 2,3-dioxygenase is important for controlling the immune system during normal and disease conditions including pregnancy, cancer, inflammation and infectious disease. Despite its importance little is known about how this enzyme is controlled. This project will provide important new insights into how this enzyme is regulated. Such fundamental scientific information can discover new ways in which to alter the enzyme's activity in order to modulate immune responses.
Regulation Of SRC-Family And Focal Adhesion Kinase Function
Funder
National Health and Medical Research Council
Funding Amount
$381,338.00
Summary
Cells in our bodies stick to one another and to the cementing material called extracellular matrix surrounding them. An ezyme called focal adhesion kinase (FAK) is a major regulator of cell stickiness. It can catalyze the covalent attachment of a chemical group called phosphate to specific cellular protein. This proposal aims at studying how FAK is regulated by insulin stimulation and how FAK is regulated by a tumour suppressor called PTEN. Results of the study will shed light on how abberration ....Cells in our bodies stick to one another and to the cementing material called extracellular matrix surrounding them. An ezyme called focal adhesion kinase (FAK) is a major regulator of cell stickiness. It can catalyze the covalent attachment of a chemical group called phosphate to specific cellular protein. This proposal aims at studying how FAK is regulated by insulin stimulation and how FAK is regulated by a tumour suppressor called PTEN. Results of the study will shed light on how abberrations in the regulation and PTEN contribute to the development of development defects, heart attack, and the spreading of cancer cells.Read moreRead less