Understanding Changes In The Mammalian Prenylome Induced By Statins And Prenyltransferase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Prenylation, the covalent attachment of isoprenoid lipids to proteins, is widespread in mammalian cells. Essential for a protein's normal function, it contributes to the progression of cancer and inflammation. We have developed a novel technology to identify all prenylated proteins in the cell. Aided by this method, we will analyse the effect of statins and anti-cancer drugs on protein prenylation. This will provide guidance in identifying a more effective clinical use for them.
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Activation And Inhibition Of The Plasminogen/Plasmin System
Funder
National Health and Medical Research Council
Funding Amount
$800,663.00
Summary
Plasmin is crucial enzyme present in blood plasma that functions in clot dissolution, inflammation, tissue remodeling, and wound healing. We aim to study how this enzyme system is controlled, by studying its interaction with receptors, co-factors and inhibitors. The information we gain will help drive the development of new generation therapeutics for the fine control of plasmin function in clotting disease, bleeding and inflammation.
Understanding The Role Of The Putative Phospholipid Translocase ATP11c In B Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$455,153.00
Summary
The immune system protects humans against recurrent infections with a wide range of pathogens. Formation of antibodies is a crucial element of the immune response. Defects in the production of antibodies can lead to recurrent and often life-threatening infections. This project seeks to understand a genetic defect in mice resulting in an almost complete absence of antibody producing cells, thereby causing a disease that is similar to some forms of human immunodeficiency.
The Molecular Mechanism Of Ion-coupled Transport In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$441,407.00
Summary
Cells in the brain communicate through chemical signals called neurotransmitters. Neurotransmitter transporters reside in the membranes of cells and are responsible for regulating levels of these chemicals in the brain. They play an important role in the normal function of the human brain but their dysfunction is responsible for many diseases including Alzheimer's disease and motor neuron disease. It is crucial to understand how these proteins work in both normal and disease states.
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.
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.
Regulation Of Neural Progenitor Cell Self-renewal By The RNA-binding Protein ZFP36L1 During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$345,401.00
Summary
The timely differentiation of neural stem cells is critical during development, and the unrestrained proliferation of neural stem cells in the adult can lead to deadly brain cancers such as glioma. At present our understanding of the key molecules that regulate neural stem cell behaviour during these processes remains limited. In this proposal we will investigate the molecular determinants underpinning neural stem cell biology, both within the developing brain, and within glioma.
Characterising Novel Alternative Splicing Networks That Promote Tumour Cell Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$609,329.00
Summary
During cancer progression, tumour cells can change their properties and become more aggressive and resistant to therapies. We have identified an important regulator of this tumour cell transition, called “Quaking”, which causes widespread changes in gene splicing. We aim to investigate how "Quaking" causes changes in gene splicing and what the effects of these splicing changes are in tumour cells.
Structural And Functional Studies On RNA Nuclear Retention Mediated By Paraspeckles: A Novel Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$290,978.00
Summary
Dynamic interactions between proteins and nucleic acids are essential process in gene regulation, where aberrant regulation leads to various diseases including cancers. The project aims to examine the interactions between paraspeckle proteins and nucleic acid molecules via determination of the structures of protein-nucleic acid complexes at the atomic level. The results will provide a better understanding of a recently discovered gene regulation mechanism and a basis for new gene therapy.