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
Neural circuits that mediate fear conditioning and extinction. Understanding of how the brain processes, stores and retrieves information and produces behavioural outcomes is in its infancy. This project will use electrophysiology and molecular techniques to understand the circuits that mediate one form of emotional learning.
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.
Read moreRead less
Muscle fibre excitability and calcium regulation in skeletal muscle of amphibians and mammals. The fundamental role of skeletal muscle is posture and movement. Essential for this is a specialised cell structure and a complex regulation of function. This project will define key aspects of muscle structure and functional regulation crucial to developing targets for improving function under stressed states such as fatigue, disease and age.
Sarcoplasmic reticulum-mitochondrial functional interactions in muscle. Muscle in the body of animals and human has the ability to adapt to stress placed on it, to improve performance. This allows new physical tasks that have been unfamiliar to become easier. One form of stress on the muscle is the demand to work longer without fatigue. This can be important for animal survival or athletes training for sport. A single session of intense muscle contractions can lead to the muscle increasing its c ....Sarcoplasmic reticulum-mitochondrial functional interactions in muscle. Muscle in the body of animals and human has the ability to adapt to stress placed on it, to improve performance. This allows new physical tasks that have been unfamiliar to become easier. One form of stress on the muscle is the demand to work longer without fatigue. This can be important for animal survival or athletes training for sport. A single session of intense muscle contractions can lead to the muscle increasing its capacity for endurance within 24 hrs. This project aims to examine this phenomenon in animals and human to decipher the mechanism involved in the beneficial muscle changes experienced in such a brief time. It will provide benefits such as the potential to manipulate human muscle condition and animal muscle (meat) quality.Read moreRead less
Cellulose-based composites as models for primary plant cell walls of cereals and grasses. Cereals and grasses are the lynchpins of the Australian Agri-Food industry. Cell walls provide shape, form and barrier properties to the plant and are the basis for both post-harvest mechanical properties and direct nutritional benefits. There is as yet no validated model for the molecular assembly, architecture and mechanical behaviour of cereal/grass cell walls. This project aims to derive such a model, s ....Cellulose-based composites as models for primary plant cell walls of cereals and grasses. Cereals and grasses are the lynchpins of the Australian Agri-Food industry. Cell walls provide shape, form and barrier properties to the plant and are the basis for both post-harvest mechanical properties and direct nutritional benefits. There is as yet no validated model for the molecular assembly, architecture and mechanical behaviour of cereal/grass cell walls. This project aims to derive such a model, so that predictions can be made concerning the effects of tailoring either plant composition (e.g. at the gene level) or post-harvest treatment in order to achieve desired plant or food properties. The findings will also be relevant to understanding how individual features of cell walls affect digestibility and nutritional properties.Read moreRead less
Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractab ....Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of cell and developmental biology.Read moreRead less
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