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
Membrane Attachment And Components Of The Ca2+ -triggered Release Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$386,498.00
Summary
Understanding and harnessing the fundamental cellular process of secretion will provide a wealth of new approaches to addressing problems associated with aging & disorders that are major health care burdens (e.g. neurodegeneration & diabetes). Understanding the vesicle docked state, and the contributions of different molecular components to the release process provides for unique insights into the underlying molecular mechanisms, thereby enabling safe, targeted control of this critical process.
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
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
Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothe ....Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothesis that dual water and ion channel functions of AQP1 are needed for movement, using migration assays in cells with wild type and mutant AQP1, and selective pharmacological agents developed by the project team to dissect the essential channel properties that enable rapid migration in cancer and stem cells. The project seeks to build knowledge of AQP roles in development, regeneration and surveillance, potentially improving health care by revealing pathways in migration disorders such as metastasis.Read moreRead less
Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers i ....Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers in kidney and brain, and in allowing red blood cells to maintain the classic disk-shape needed for optimal transport. Outcomes will define features of aquaporin-1 that provide these functions, using molecular, optical and pharmacological tools. Results will define aquaporin channel properties that enable optimal cellular function.Read moreRead less
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
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
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