Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The stud ....Conductance states of a brain glutamine transporter. Brain transporters are the target for many neuroactive drugs that are used to treat anxiety, depression and other psychotic disorders. Transport processes are also targeted to deliver neurotransmitter precursors to the brain to treat disorders such as Parkinson's disease. In this project we will study a transport process crucial for the function of neurons that release glutamate and GABA (gamma-aminobutyric acid) as neurotransmitters. The study of this transport process will be important for understanding disorders like epilepsy and other disorders affecting neuronal excitability.Read moreRead less
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
The role of turgor in hyphal extension of the Ascomycete Neurospora crassa. Cellular expansion is an absolute necessity during the growth and development of plants and fungi. This process relies heavily upon the accumulation of inorganic ions. Osmotically driven water influx then creates the hydrostatic pressure that underlies the increase in cell volume. Cellular expansion is normally asymmetric and localised in one small region, such as hyphal tip. How does the cell maintain the turgor that dr ....The role of turgor in hyphal extension of the Ascomycete Neurospora crassa. Cellular expansion is an absolute necessity during the growth and development of plants and fungi. This process relies heavily upon the accumulation of inorganic ions. Osmotically driven water influx then creates the hydrostatic pressure that underlies the increase in cell volume. Cellular expansion is normally asymmetric and localised in one small region, such as hyphal tip. How does the cell maintain the turgor that drives expansion? How is expansion controlled spatially? These questions will be addressed in this project by comprehensive study of ion transport processes in a model organism, Neurospora crassa, using osmotic sensitive and transport mutants.Read moreRead less
In situ measurements of the electrostatic properties inside photosynthetic reaction centres: correlation with the energy conversion function of the protein. The photochemical reaction centre is a key protein complex involved in energy conversion. It converts solar energy into chemical energy as a transmembrane charge separation. Coupling of electron and proton transfer is catalysed at the level of a ubiquinone cofactor. In order to understand how the redox properties of this cofactor are fine tu ....In situ measurements of the electrostatic properties inside photosynthetic reaction centres: correlation with the energy conversion function of the protein. The photochemical reaction centre is a key protein complex involved in energy conversion. It converts solar energy into chemical energy as a transmembrane charge separation. Coupling of electron and proton transfer is catalysed at the level of a ubiquinone cofactor. In order to understand how the redox properties of this cofactor are fine tuned by the protein environment, we plan to probe the ubiquinone site using a voltage-sensitive fluorescent dye. This exciting multidisciplinary project will contribute to the understanding of how protein matrices influence and govern the midpoint redox potential of their cofactors and the environments of theirRead moreRead less
The response of mitochondria to oxidative stress in plants. Crops encounter many situations in their environment which place them under stress. Reactive oxygen molecules produced in these situations act as messengers to trigger defence mechanisms but also cause cellular damage. Mitochondria are the subcellular compartments involved in energy production and are essential for plant development and growth. However, they also have been implicated in the response of plants to stress and pathogen atta ....The response of mitochondria to oxidative stress in plants. Crops encounter many situations in their environment which place them under stress. Reactive oxygen molecules produced in these situations act as messengers to trigger defence mechanisms but also cause cellular damage. Mitochondria are the subcellular compartments involved in energy production and are essential for plant development and growth. However, they also have been implicated in the response of plants to stress and pathogen attack, and in production of reactive oxygen molecules. This proposal seeks to investigate how mitochondria are involved in these processes, focusing on the role of terminal oxidases. Potential outcomes include crops better able to cope with environmental stress.Read moreRead less
Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic ....Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic species of alpha-proteobacteria provides for a timely advance in our knowledge of their biology: other species of alpha-proteobacteria were amongst the first organisms trialled for biological weapons by the USA and the former Soviet Union, and those pathogenic species are rated as Class 3 organisms.Read moreRead less
Increasing the Efficiency of Biomolecular Simulations. This program will extend the range of biomolecular systems that can be modelled with near atomistic precision. It will provide a better understanding of the structure and function of proteins involved in the regulation of membrane fusion and fission as well as shedding light on the assembly of large-scale protein-protein and protein-membrane complexes in general. The work will help place Australia at the forefront of developing simulation t ....Increasing the Efficiency of Biomolecular Simulations. This program will extend the range of biomolecular systems that can be modelled with near atomistic precision. It will provide a better understanding of the structure and function of proteins involved in the regulation of membrane fusion and fission as well as shedding light on the assembly of large-scale protein-protein and protein-membrane complexes in general. The work will help place Australia at the forefront of developing simulation techniques in biomolecular systems, which are widely used within the chemical and pharmaceutical industries. It will also provide opportunities for the training and development of young Australian researchers with top European laboratories. Read moreRead less
Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology ....Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology, Ca2+ regulation and optical membrane potentiometry allow us to monitor early changes in disease on a (sub)cellular level. Experiments on Ca2+ regulation and ion channel function in muscle with different cholesterol membrane contents will help to understand pathomechanisms in high cholesterol diseases, e.g. obesity, on the membrane level long before cardiovascular effects become prominent.Read moreRead less
Combining the soft with the hard: The assembly of artificial cell membranes on porous semiconductors. The platform technologies developed in this project will have a wide range of applications. They will reveal new insights into drug-membrane and drug-protein interactions underpinning development of a new generation of drugs acting on transmembrane proteins that are linked to a wide range of diseases. The development of membrane-based biosensing devices targeting ion channels, membrane active pe ....Combining the soft with the hard: The assembly of artificial cell membranes on porous semiconductors. The platform technologies developed in this project will have a wide range of applications. They will reveal new insights into drug-membrane and drug-protein interactions underpinning development of a new generation of drugs acting on transmembrane proteins that are linked to a wide range of diseases. The development of membrane-based biosensing devices targeting ion channels, membrane active peptides or toxins which can be applied to biomedical diagnostics, biotoxin detection, environmental and food control will be readily achievable. This international interdisciplinary nanobiotechnology programme and its outcomes will enhance Australia's abilities in frontier technologies and build research strength in nanobiotechnology.Read moreRead less
Pharmacological and biochemical characterisation of Australian mygalomorph spider venoms. This project will increase our limited knowledge of Australian mygalomorph venoms by isolation, identification and characterisation of novel toxins in theraphosid and Northern mouse-spider venoms. Thereby, the scientific basis for the treatment of mygalomorph spider bites might be improved. Secondly, new insights into pharmacology and the potential development of novel therapeutics and molecular probes of t ....Pharmacological and biochemical characterisation of Australian mygalomorph spider venoms. This project will increase our limited knowledge of Australian mygalomorph venoms by isolation, identification and characterisation of novel toxins in theraphosid and Northern mouse-spider venoms. Thereby, the scientific basis for the treatment of mygalomorph spider bites might be improved. Secondly, new insights into pharmacology and the potential development of novel therapeutics and molecular probes of target molecules might be expected.Read moreRead less