A rational approach to a high-resolution structure of the multidrug transporter EmrE. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. Multidrug transporters are membrane proteins responsible for antibiotic resistance in humans. A high-resolution structure of a multidrug resistance protein, together with comprehensive biochemical characterization, w ....A rational approach to a high-resolution structure of the multidrug transporter EmrE. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. Multidrug transporters are membrane proteins responsible for antibiotic resistance in humans. A high-resolution structure of a multidrug resistance protein, together with comprehensive biochemical characterization, would enable a detailed understanding of how these protein functions. Potentially it could also aid in the development of specific inhibitors that would prevent EmrE (and perhaps other similar proteins) from carry out its harmful mission. Read moreRead less
Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional character ....Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional characterisation of this class of potassium channels is of great importance as they are interesting targets for new therapeutic developments. Advancement of knowledge in the structure and function of these channels will underpin drug targeting that will aid preventative healthcare, allowing Australians to age well and age productively.Read moreRead less
Electro-active and migratory peptides in lipid bilayers: NMR and biophysical studies. All living things are characterized by the separation of inner space from the surrounding medium by a self-assembling membrane. Selective entry and exit of water, ions and solutes is a defining feature of each type of cell. Some proteins sense the voltage difference across the cell membrane and open or close in response to voltage changes. Others, like bacterial toxins assemble in the membrane as pores, while o ....Electro-active and migratory peptides in lipid bilayers: NMR and biophysical studies. All living things are characterized by the separation of inner space from the surrounding medium by a self-assembling membrane. Selective entry and exit of water, ions and solutes is a defining feature of each type of cell. Some proteins sense the voltage difference across the cell membrane and open or close in response to voltage changes. Others, like bacterial toxins assemble in the membrane as pores, while other peptides migrate across the membrane piggy-backing their peptide cargo. The aim is to understand the molecular mechanisms in examples of these membrane-active peptides and proteins with a view to enabling rational intervention into their operation in situ in normal and disease states.Read moreRead less
NMR studies of membrane proteins and peptides in novel amphiphilic mesophases. Membrane proteins are the next frontier in structural biology. Our goal is the structural and mechanistic characterization of the proteins and peptides from platypus venom and a cardiac potassium ion channel, HERG, that has a particular role in the suppression of cardiac arrhythmias. To do this we will refine and develop methods using amphiphilic mesophases and micelles and state-of-the-art NMR spectroscopy. Electrop ....NMR studies of membrane proteins and peptides in novel amphiphilic mesophases. Membrane proteins are the next frontier in structural biology. Our goal is the structural and mechanistic characterization of the proteins and peptides from platypus venom and a cardiac potassium ion channel, HERG, that has a particular role in the suppression of cardiac arrhythmias. To do this we will refine and develop methods using amphiphilic mesophases and micelles and state-of-the-art NMR spectroscopy. Electrophysiological analysis of ion channels and interactions with toxins will relate NMR structures to function. The NMR methodologies we develop will have broad applicability to membrane proteins in general.
Read moreRead less
The Study of Pretreatment Options for Composite Fouling of Reverse Osmosis Membranes Used in Water Treatment and Production. It is recognised worldwide that fouling is a major impediment in operation of Reverse Osmosis units used for production, purification and treatment of water. This project is aimed at studying pre-treatment options for composite fouling which is the main type of fouling present in RO units by using both model feed systems and actual field water. The project outcomes are to ....The Study of Pretreatment Options for Composite Fouling of Reverse Osmosis Membranes Used in Water Treatment and Production. It is recognised worldwide that fouling is a major impediment in operation of Reverse Osmosis units used for production, purification and treatment of water. This project is aimed at studying pre-treatment options for composite fouling which is the main type of fouling present in RO units by using both model feed systems and actual field water. The project outcomes are to understand and develop pre-treatment strategies and to use those to develop a hybrid pre-treatment technology. This project will significantly impact water production in general and its outcomes will have far-reaching implications in treatment of water both within Australia and globally.Read moreRead less
The Boron Rejection by RO Membranes in presence of Calcium Carbonate and Magnesium Hydroxide. Water scarcity in various parts of the world demands the use of available saline waters for production of potable water. Reverse Osmosis membranes have been used as a means of achieving this objective. Fouling is a major impediment in operation of reverse osmosis units. The project aims to study boron removal by RO under high pH which increases the boron rejection but at the same time exacerbates compos ....The Boron Rejection by RO Membranes in presence of Calcium Carbonate and Magnesium Hydroxide. Water scarcity in various parts of the world demands the use of available saline waters for production of potable water. Reverse Osmosis membranes have been used as a means of achieving this objective. Fouling is a major impediment in operation of reverse osmosis units. The project aims to study boron removal by RO under high pH which increases the boron rejection but at the same time exacerbates composite fouling by calcium carbonate and magnesium hydroxide. Optimum pH for boron rejection will be determined and propensity of calcium carbonate and magnesium hydroxide at that pH range will be evaluated.Read moreRead less
Streamlining the dynamin epilepsy drug pipeline. Epilepsy affects up to one percent of Australia's population, yet one in three fail to respond to current medications. Our results will greatly impact on development of future epilepsy therapy. Identification of a new target for epileptic will allow better drug design to improve the potency of our lead drugs. This holds hope that new generation drugs will be more effective. The drugs are predicted to have fewer complications and side-effects. Th ....Streamlining the dynamin epilepsy drug pipeline. Epilepsy affects up to one percent of Australia's population, yet one in three fail to respond to current medications. Our results will greatly impact on development of future epilepsy therapy. Identification of a new target for epileptic will allow better drug design to improve the potency of our lead drugs. This holds hope that new generation drugs will be more effective. The drugs are predicted to have fewer complications and side-effects. The outcome has the potential to vastly improve prospects for up to 200,000 Australians. Intellectual property (IP) retained in Australia will generate future biotechnology industry. The novel chemical biological approaches will facilitate training of future generations of Australian scientists.Read moreRead less
Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal w ....Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal will receive international recognition and will encourage more research in this field, attracting international funding, and create new research opportunities. Read moreRead less
The role of floc structure in the formation of sediments and filter cakes. The project aims to understand at a fundamental level if and in what way the fractal structure of aggregates of fine particles is preserved when forming sediments and filter cakes. The effect of this structure on processes for separating solids and liquids is significant: each year, millions of dollars stand to be saved though more efficient filtration, and more efficient thickening of mineral slurries. Improved understan ....The role of floc structure in the formation of sediments and filter cakes. The project aims to understand at a fundamental level if and in what way the fractal structure of aggregates of fine particles is preserved when forming sediments and filter cakes. The effect of this structure on processes for separating solids and liquids is significant: each year, millions of dollars stand to be saved though more efficient filtration, and more efficient thickening of mineral slurries. Improved understanding allows intelligent design of flocculation systems to optimise the performance of downstream solid - liquid separation processes, maximising economic and environmental returns.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100096
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
A unique soft matter high-performance scanning probe microscopy (HP-SPM) facility. Soft matter research touches every aspect of our lives as it covers materials from the range of plastics found in cars, television sets and other mass-manufactured products, to new medical materials for tissue engineering and sensors. The proposed facility will enable Australia's leading scientists in this area to understand better how soft matter, including both biological and new advanced soft materials, behave ....A unique soft matter high-performance scanning probe microscopy (HP-SPM) facility. Soft matter research touches every aspect of our lives as it covers materials from the range of plastics found in cars, television sets and other mass-manufactured products, to new medical materials for tissue engineering and sensors. The proposed facility will enable Australia's leading scientists in this area to understand better how soft matter, including both biological and new advanced soft materials, behaves on the nano-scale level. This will put Australian researchers and engineers in a leading position for developing new treatments against cancer and other diseases, as well as harnessing the power of biology for application in areas such as waste treatment and energy production.Read moreRead less