How triadin and junctin communicate with ryanodine receptors deep within a calcium store to determine skeletal muscle contraction. The project results will provide a platform for muscle relaxants and other drugs that will specifically target either the heart or skeletal muscle and will have applications in the livestock, veterinary and pharmaceutical Industries. The project falls within the National Research Priorities of Promoting and Maintaining Good Health and Frontier Technologies for Buil ....How triadin and junctin communicate with ryanodine receptors deep within a calcium store to determine skeletal muscle contraction. The project results will provide a platform for muscle relaxants and other drugs that will specifically target either the heart or skeletal muscle and will have applications in the livestock, veterinary and pharmaceutical Industries. The project falls within the National Research Priorities of Promoting and Maintaining Good Health and Frontier Technologies for Building and Transforming Australian Industries, as well as the national priority goal of Ageing well, Ageing Productively. The project will be of national benefit in training undergraduate students, PhD students and a postdoctoral fellow in state-of-the-art techniques in an internationally competitive research field.Read moreRead less
SKELETAL MUSCLE: REVERSIBLE TEMEPERATURE-INDUCED UNCOUPLING OF CONTRACTION FROM THE ACTIVATOR Ca2+ AND TUBULAR SYSTEM ROLES IN MUSCLE FUNCTION REGULATION. Skeletal muscles represent the largest organ in the body of vertebrates and are responsible for major functions including maintaining posture and locomotion. Skeletal muscles are also a major source of heat production. The project focuses on temperature-induced effects on the ability of the skeletal muscle to contract in warm blooded animals, ....SKELETAL MUSCLE: REVERSIBLE TEMEPERATURE-INDUCED UNCOUPLING OF CONTRACTION FROM THE ACTIVATOR Ca2+ AND TUBULAR SYSTEM ROLES IN MUSCLE FUNCTION REGULATION. Skeletal muscles represent the largest organ in the body of vertebrates and are responsible for major functions including maintaining posture and locomotion. Skeletal muscles are also a major source of heat production. The project focuses on temperature-induced effects on the ability of the skeletal muscle to contract in warm blooded animals, including marsupials, and on the complex roles played by a cellular structure unique to the muscle fibre, the tubular system, with respect to regulation of muscle function at physiological temperatures. The project will test hypotheses that will have far-reaching implications for muscle physiology, cell biology and evolutionary biology.Read moreRead less
A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of the ....A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of their ion channels (selective protein pores) and receptors contribute to the odorant-induced generation of electrical activity, which mediates our sense of smell (olfaction). The project has specific relevance for understanding olfaction, as well as relevance for other sensory systems and other ion channels.Read moreRead less
REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that th ....REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that the proteins also bind to each other and that calsequestrin regulates Ca2+ release from the stores through the ryanodine receptor ion channel. This regulation is likely to be important in conserving store calcium during stress or fatigue.Read moreRead less
Resurgent Sodium Currents in Peripheral Nerve Axons and Sensory Neurones. This project seeks evidence that unusual gating of sodium channels contributes to the hyperexcitability that results in spontaneous impulse activity in sensory axons. It asks whether axons normally behave as if they have this gating mode, whether it can be induced, whether any such behaviour is more prominent with sensory axons than motor, and whether the current can be measured directly in sensory neurones. The project is ....Resurgent Sodium Currents in Peripheral Nerve Axons and Sensory Neurones. This project seeks evidence that unusual gating of sodium channels contributes to the hyperexcitability that results in spontaneous impulse activity in sensory axons. It asks whether axons normally behave as if they have this gating mode, whether it can be induced, whether any such behaviour is more prominent with sensory axons than motor, and whether the current can be measured directly in sensory neurones. The project is the first to involve correlation of patch-clamp recordings with the behaviour of intact axons. Its outcomes will affect thought about sodium channel behaviour and may alter approaches to disorders of axonal excitability.Read moreRead less
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
A new model for secreton in epithelial cells. This proposal sets out to test a new model for secretion that we have developed in the light of recent experimental data. The project outcomes will advance our understanding of normal processes of secretion and may be important in understanding disease. We will develop cutting-edge techniques of microscopy which will place Australia at the forefront of this exciting field. The project will bring benefit to the Australian scientific community through ....A new model for secreton in epithelial cells. This proposal sets out to test a new model for secretion that we have developed in the light of recent experimental data. The project outcomes will advance our understanding of normal processes of secretion and may be important in understanding disease. We will develop cutting-edge techniques of microscopy which will place Australia at the forefront of this exciting field. The project will bring benefit to the Australian scientific community through interactions and collaborations with other scientists in Australia and internationally and will benefit early-career scientists, training them in novel methods and allowing them to develop their research expertise and profile and enabling them to compete on the world science stage. Read moreRead less
ION CHANNELS FORMED BY SMALL PROTEINS FROM VIRUSES. Movements of ions across cell membranes through protein ion channels are essential for normal cell function. We have found that some small proteins from viruses can form ion channels. Studying these simple channels should give us clues about the function of more complex channels, such as those in the brain, as well as giving us information about the viruses themselves. We will test whether a small protein from Ross River virus forms ion channel ....ION CHANNELS FORMED BY SMALL PROTEINS FROM VIRUSES. Movements of ions across cell membranes through protein ion channels are essential for normal cell function. We have found that some small proteins from viruses can form ion channels. Studying these simple channels should give us clues about the function of more complex channels, such as those in the brain, as well as giving us information about the viruses themselves. We will test whether a small protein from Ross River virus forms ion channels and will also test the effects of selected mutations in proteins from influenza and AIDS viruses that we have shown previously to form ion channels.Read moreRead less
Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unkno ....Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unknown membrane proteins that move sucrose at high rates between cells and discover their transport properties. Expected outcomes are to better understand mechanisms and regulation of sucrose transport and hence provide novel opportunities to enhance crop yield. The project will foster a productive international collaboration.Read moreRead less
Multifunctional channels as key components of biotrophic interfaces in legumes. In legumes there are two types of membrane interfaces between different genomes that are critical for growth and yield (nitrogen fixation and seed loading), which require cell-signalling pathways to control nutrient exchange. The membranes of these interfaces contain specialised proteins that form multifunctional channels through which water, uncharged molecules and electrolytes move. These channels are likely to be ....Multifunctional channels as key components of biotrophic interfaces in legumes. In legumes there are two types of membrane interfaces between different genomes that are critical for growth and yield (nitrogen fixation and seed loading), which require cell-signalling pathways to control nutrient exchange. The membranes of these interfaces contain specialised proteins that form multifunctional channels through which water, uncharged molecules and electrolytes move. These channels are likely to be responsible for supporting the bulk of transported nutrients and in controlling their exchange. We aim to discover how these channels function in nitrogen fixation and seed loading with a view to developing new technologies that may enhance crop productivity.Read moreRead less