Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, elec ....G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, electrical and fluorescence techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in integrating diverse extracellular stimuli and neuronal excitablility in the peripheral nervous system.Read moreRead less
Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thor ....Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thorough characterisation of a novel pathway that is potentially crucial in the development, homeostasis and regeneration of the nervous system. Disruption of normal function of this system may underlie the hyperexcitability observed in mannu neurodegenerative conditions.Read moreRead less
Physiological Thermoregulation and Cardiovascular Function in Reptiles. This project will be important in advancing the concept of physiological thermoregulation in reptiles from a descriptive to a mechanistic basis, thereby providing a better conceptual framework within which the evolutionary processes and selection pressures acting on modern animals and their ancestors can be evaluated.
Benefits of conducting this research will include:
maintaining the high international profile of Aust ....Physiological Thermoregulation and Cardiovascular Function in Reptiles. This project will be important in advancing the concept of physiological thermoregulation in reptiles from a descriptive to a mechanistic basis, thereby providing a better conceptual framework within which the evolutionary processes and selection pressures acting on modern animals and their ancestors can be evaluated.
Benefits of conducting this research will include:
maintaining the high international profile of Australian comparative physiology;
the training of post-graduate students, both Honours and Ph.D.s;
stimulating collaboration between two of Australia's research intensive universities (Sydney and Queensland);
and show-casing Australia's impressive reptilian fauna.
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Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also disco ....Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also discovered that this cross-talk between prostaglandin- and cytokine-receptor signalling pathways occurs in preadipocyte and breast cell lines and propose that this research will serve as a paradigm for understanding how sensitivity to cytokines can be controlled at a molecular level.Read moreRead less
Calcium regulation in the skeletal muscle triad and along the fibre. The fundamental role of skeletal muscle is posture and movement. Alterations in the normal way calcium regulates skeletal muscle function in fatigue, age and disease states causes loss of normal function. Preventing or controlling these changes is a key therapeutic aim. However, we currently lack full understanding of key mechanisms of calcium regulation in healthy skeletal muscle. This project will define key aspects of cal ....Calcium regulation in the skeletal muscle triad and along the fibre. The fundamental role of skeletal muscle is posture and movement. Alterations in the normal way calcium regulates skeletal muscle function in fatigue, age and disease states causes loss of normal function. Preventing or controlling these changes is a key therapeutic aim. However, we currently lack full understanding of key mechanisms of calcium regulation in healthy skeletal muscle. This project will define key aspects of calcium regulation that could be crucial to developing targets for improving function of skeletal muscle under stressed states.Read moreRead less
Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during developmen ....Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during development, test whether synaptic activation of receptors is required for these changes and define the pattern of activity-dependent changes in gene expression necessary for developmental changes in synaptic transmission. Understanding this interaction between synaptic phenome and activity-dependent genomic expression will expand our understanding of brain development and function.Read moreRead less
The inhibition of muscle disuse atrophy in burrowing frogs. Prolonged muscle disuse, as a consequence of limb immobilisation, extended bed-rest or space travel, can lead to pathological changes resulting in muscle wasting. By examining a unique Australian frog that burrows underground and remains immobile for 9-12 months, and which shows no muscle wasting, we will significantly advance our understanding of the physiological mechanisms that inhibit muscle atrophy.
Benefits of conducting this r ....The inhibition of muscle disuse atrophy in burrowing frogs. Prolonged muscle disuse, as a consequence of limb immobilisation, extended bed-rest or space travel, can lead to pathological changes resulting in muscle wasting. By examining a unique Australian frog that burrows underground and remains immobile for 9-12 months, and which shows no muscle wasting, we will significantly advance our understanding of the physiological mechanisms that inhibit muscle atrophy.
Benefits of conducting this research will include:
- understanding the role of antioxidants and endogenous opioids in reducing muscle wasting
- training of postgraduate students
- stimulating collaboration between The University of Queensland and CSIRO Livestock Industries.Read moreRead less
The evolution of energy metabolism in ectotherms. Metabolic rate is the rate at which organisms take up, transform, and expend energy and materials. The primary outcome of this initiative is a comprehensive understanding of the effect of climate on the metabolic rate of ectothermic vertebrates, including goannas, fish and toads. Our research will encompass aquatic and terrestrial environments; temperate and tropical habitats; and include both iconic native species and alien invasive ones. We se ....The evolution of energy metabolism in ectotherms. Metabolic rate is the rate at which organisms take up, transform, and expend energy and materials. The primary outcome of this initiative is a comprehensive understanding of the effect of climate on the metabolic rate of ectothermic vertebrates, including goannas, fish and toads. Our research will encompass aquatic and terrestrial environments; temperate and tropical habitats; and include both iconic native species and alien invasive ones. We seek to understand not only how and why species in these environments vary in their metabolic rate, but also the consequences of this variation. Such knowledge will be important in understanding how climate change does and will affect animals and in predicting its consequences.Read moreRead less
Regulation of salt gland activity in the estuarine crocodile: phenotypic plasticity and control mechanisms. The estuarine crocodile excretes excess sodium and chloride ions through salt glands located on the tongue, enabling the crocodile to live in seawater. This study will investigate the regulation of salt gland secretory capacity and activity, by examining both the phenotypic plasticity of the gland to changes in environmental salinity and diet, and by determining the neural/humoral mech ....Regulation of salt gland activity in the estuarine crocodile: phenotypic plasticity and control mechanisms. The estuarine crocodile excretes excess sodium and chloride ions through salt glands located on the tongue, enabling the crocodile to live in seawater. This study will investigate the regulation of salt gland secretory capacity and activity, by examining both the phenotypic plasticity of the gland to changes in environmental salinity and diet, and by determining the neural/humoral mechanisms controlling secretory rate. In vivo measurements of blood flow and salt gland secretory rate, together with perfused gland preparations will reveal extrinsic and intrinsic factors controlling salt gland activity and the degree of coupling between blood flow and secretory rate.Read moreRead less