Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales ....Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales with molecular dynamics at small distances and shorter times. Applications to both membrane proteins (blocking of ion channels by toxins and drugs) and globular proteins (ligand binding to receptors and protein association) will be considered.Read moreRead less
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 geochemical role of iron in basaltic magmatism and planetary differentiation: an experimental study. The amount of Fe in primitive terrestrial basalts is surprisingly variable. The reasons for this are poorly understood, but could include melting of Fe-enriched refertilized mantle sources, increasing partitioning of FeO into the melt with depth of melting, or oxidation of some FeO to Fe2O3. An experimental investigation of the effects of Fe both as 2+ and 3+ on the partial melting of model ....The geochemical role of iron in basaltic magmatism and planetary differentiation: an experimental study. The amount of Fe in primitive terrestrial basalts is surprisingly variable. The reasons for this are poorly understood, but could include melting of Fe-enriched refertilized mantle sources, increasing partitioning of FeO into the melt with depth of melting, or oxidation of some FeO to Fe2O3. An experimental investigation of the effects of Fe both as 2+ and 3+ on the partial melting of model mantle material should help resolve this problem, while also providing the fundamental thermodynamic data needed to calibrate a general model for upper mantle phase relations.Read moreRead less
Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preven ....Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preventative health perspective, the investigation of platelet calcium signalling will greatly accelerate the development of new pharmaceuticals to tackle acute and chronic cardiovascular diseases, such as stroke, heart attack and artherosclerosis. Read moreRead less
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Understanding the deep mantle: experimental petrology at very high pressures. The great processes that shape the Earth at its surface, including plate tectonics and continental drift, can only be understood by appreciating how the interior of the Earth works. However, studying the deep Earth is difficult because of the enormous pressures and temperatures involved. This research proposes to simulate conditions in the Earth's lower mantle (that is, below 670 km in depth) by making use of an Austra ....Understanding the deep mantle: experimental petrology at very high pressures. The great processes that shape the Earth at its surface, including plate tectonics and continental drift, can only be understood by appreciating how the interior of the Earth works. However, studying the deep Earth is difficult because of the enormous pressures and temperatures involved. This research proposes to simulate conditions in the Earth's lower mantle (that is, below 670 km in depth) by making use of an Australian invented diamond-based ceramic, to double the pressure at which experiments can be performed. The information gained from this fundamental research will help predict how giant ore bodies form. The development of the high-pressure apparatus will also aid material scientists in their quest for novel materials.Read moreRead less
Water storage in the earth's mantle - understanding the process of OH incorporation in olivine. The amount of water in the Earth's mantle is thought to be sufficient to replace the surface oceans more than ten times. Whether this water exists in a fluid, melt, or mineral is important for understanding a range of mantle properties. The entire upper mantle water budget may be accommodated at defect sites in the mineral olivine. However, defects found in natural olivine do not correspond to thos ....Water storage in the earth's mantle - understanding the process of OH incorporation in olivine. The amount of water in the Earth's mantle is thought to be sufficient to replace the surface oceans more than ten times. Whether this water exists in a fluid, melt, or mineral is important for understanding a range of mantle properties. The entire upper mantle water budget may be accommodated at defect sites in the mineral olivine. However, defects found in natural olivine do not correspond to those produced
experimentally. Therefore, previous conclusions on water storage in the mantle are questionable. To address this problem the mechanism of water incorporation in olivine will be investigated using experimental petrology and spectroscopy.Read moreRead less
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
Experimental constraints on Platinum-Group Element geochemistry: developing lithogeochemical exploration tools for nickel-sulfides in mafic and ultramafic systems. Nickel contributes approximately $2 billion per year to Australia's export income. Currently 80% of that is coming from sulfide deposits, which are expected to be exhausted within thirty years barring significant new discoveries. Discovery rates have been declining for two decades, as the 'easy' targets have been found, despite a broa ....Experimental constraints on Platinum-Group Element geochemistry: developing lithogeochemical exploration tools for nickel-sulfides in mafic and ultramafic systems. Nickel contributes approximately $2 billion per year to Australia's export income. Currently 80% of that is coming from sulfide deposits, which are expected to be exhausted within thirty years barring significant new discoveries. Discovery rates have been declining for two decades, as the 'easy' targets have been found, despite a broad increase in nickel exploration expenditure to current levels of around $50 million per year. There is a pressing need for new data sets and techniques to allow industry to target new discoveries based on limited drill sampling of potential host rocks. This project forms part of a broader program to harness the igneous geochemistry of the platinum group elements as a powerful pathfinder in nickel exploration.Read moreRead less