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
Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operati ....Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operation and seeking cures for diseases caused by their malfunction. This project aims to develop accurate ion-protein-water interactions for permeation models based on stochastic and molecular dynamics simulations using both classical and quantum mechanical methods.Read moreRead less
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
Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production ....Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production and the structure/function of the solar powerhouse of plants (chloroplasts), and addresses fundamental questions at the interface of biology and physics. The research explores chloroplasts as a manifestation of the all-pervading Second Law of Thermodynamics, advancing Australia's contribution to basic science and helping to train researchers.Read moreRead less
What limits CO2 diffusion inside leaves? Dissecting the diffusion path with Arabidopsis mutants. Human induced increase in atmospheric carbon dioxide is now generally accepted as contributing to global warming. Forecasting our future impact relies on models of terrestrial photosynthesis which use a signature in the atmosphere created by plants when they discriminate against the heavy stable isotope of carbon during photosynthesis. Discrimination between isotopes is affected by carbon dioxide dif ....What limits CO2 diffusion inside leaves? Dissecting the diffusion path with Arabidopsis mutants. Human induced increase in atmospheric carbon dioxide is now generally accepted as contributing to global warming. Forecasting our future impact relies on models of terrestrial photosynthesis which use a signature in the atmosphere created by plants when they discriminate against the heavy stable isotope of carbon during photosynthesis. Discrimination between isotopes is affected by carbon dioxide diffusion within leaves and key steps in this process will be identified through the use of Arabidopsis mutants. Better representation of this process in models will improve estimates of terrestrial photosynthesis and climate change forecastsRead moreRead less
Expression and characterisation of nutrient transporters from the intracellular malaria parasite, Plasmodium falciparum. The malaria parasite invades the red blood cells of its host and this provides it with a safe haven in which to grow and replicate. Within the red blood cell, the parasite takes up nutrients and excretes metabolic wastes via specialised membrane transport proteins which are, as yet, very poorly understood. The sequencing of the malaria parasite genome has enabled us to ident ....Expression and characterisation of nutrient transporters from the intracellular malaria parasite, Plasmodium falciparum. The malaria parasite invades the red blood cells of its host and this provides it with a safe haven in which to grow and replicate. Within the red blood cell, the parasite takes up nutrients and excretes metabolic wastes via specialised membrane transport proteins which are, as yet, very poorly understood. The sequencing of the malaria parasite genome has enabled us to identify candidates for a wide variety of these proteins. The aim of this project is to establish systems in which the functional properties of these transporter proteins may be characterised in detail.Read moreRead less
Molecular Interactions of Chemical Agents with Ion-Channel Proteins. With a minimal number of functional units (proteins) viruses are able to replicate. All of these proteins are possible antiviral targets. In this project we wil1 focus on a short protein called Vpu found in membranes of the HIV-1 virus and aim to analyse the interaction of potential pore blocking compounds. It is essential to know exactly where they sit and how the overall structure of Vpu is affected. For this enterprise we wi ....Molecular Interactions of Chemical Agents with Ion-Channel Proteins. With a minimal number of functional units (proteins) viruses are able to replicate. All of these proteins are possible antiviral targets. In this project we wil1 focus on a short protein called Vpu found in membranes of the HIV-1 virus and aim to analyse the interaction of potential pore blocking compounds. It is essential to know exactly where they sit and how the overall structure of Vpu is affected. For this enterprise we will use nuclear magnetic resonance (NMR) spectroscopy. This information will serve as a springboard for future investigations of virus membrane proteins.
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Amino acids as nutrients - the molecular basis of amino acid absorption in kidney and intestine. Nutrition is a critical factor for well being and health. This is highlighted by the increase in frequency of type II diabetes and the obesity problem that all societies with a western diet face. Most studies in nutrition focus on fat and carbohydrates because of their direct involvement in obesity and diabetes. Proteins and the resulting peptides and amino acids, however, form 10-15% of our nutritio ....Amino acids as nutrients - the molecular basis of amino acid absorption in kidney and intestine. Nutrition is a critical factor for well being and health. This is highlighted by the increase in frequency of type II diabetes and the obesity problem that all societies with a western diet face. Most studies in nutrition focus on fat and carbohydrates because of their direct involvement in obesity and diabetes. Proteins and the resulting peptides and amino acids, however, form 10-15% of our nutrition. At a time where protein-rich diets are recommended to fight obesity and diabetes, it is important to understand the basis of protein absorption and metabolism. This project investigates the mechanism and mediators of amino acid absorption in kidney and intestine. Read moreRead less
Molecular analysis of photosynthetically-linked, active CO2 uptake and CO2 signal transduction by cyanobacteria (blue-green algae). Cyanobacteria (blue-green algae) have evolved a very efficient means of capturing and concentrating CO2 for photosynthetic fixation into sugars, the basic building blocks for cell growth. This process is dependent on the operation of several unique, active uptake systems for CO2 and HCO3-, with their genetic expression regulated by CO2 supply. This proposal will cap ....Molecular analysis of photosynthetically-linked, active CO2 uptake and CO2 signal transduction by cyanobacteria (blue-green algae). Cyanobacteria (blue-green algae) have evolved a very efficient means of capturing and concentrating CO2 for photosynthetic fixation into sugars, the basic building blocks for cell growth. This process is dependent on the operation of several unique, active uptake systems for CO2 and HCO3-, with their genetic expression regulated by CO2 supply. This proposal will capitalize on our progress in describing the functional genetics of this process and aims to elucidate the mechanism of active CO2 uptake and the way that cells sense the ambient CO2 concentration. The information gained is likely to be useful for designing improved crops.Read moreRead less
Structure and function of heterodimeric amino acid transporters. Recently a new family of amino acid transporters has been identified, the members of which are involved in the delivery of amino acids between cells and tissues. All members display a rather unusual structure in that they require two subunits to be functional. The main aim of this study is to investigate the interaction between large and small subunits. The study will give insight how membrane proteins form complexes in the membran ....Structure and function of heterodimeric amino acid transporters. Recently a new family of amino acid transporters has been identified, the members of which are involved in the delivery of amino acids between cells and tissues. All members display a rather unusual structure in that they require two subunits to be functional. The main aim of this study is to investigate the interaction between large and small subunits. The study will give insight how membrane proteins form complexes in the membrane and how these interactions affect the function of a complex membrane protein.Read moreRead less