Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
Rheological and Electrical Properties of Biological Soft Tissues. Research on coupling rheological and electrical properties of biological soft tissues and their composites is fundamental to medical and sport sciences, as well as the optimal design and management of smart biomedical devices and bio-microtransducers. This project aims to develop an effective rheological and electrical constitutive law and finite element implementation together with supporting experiments to reveal the novel coupl ....Rheological and Electrical Properties of Biological Soft Tissues. Research on coupling rheological and electrical properties of biological soft tissues and their composites is fundamental to medical and sport sciences, as well as the optimal design and management of smart biomedical devices and bio-microtransducers. This project aims to develop an effective rheological and electrical constitutive law and finite element implementation together with supporting experiments to reveal the novel coupling behaviour of viscoelastic and electric fields of the innovative smart biological soft tissue. These results will provide a guideline for future research in tissue engineering and help Australian biomedical science and industries improve the modern biotransducers and smart biomicro-devices.Read moreRead less
Structural studies of mammalian dimeric dihydrodiol dehydrogenase and L-xylulose reductase. The aim of the research is determine the structures and mechanisms of mammalian dimeric dihrodiol dehydrogenase and L-xylulose reductase. Mammalian dihydrodiol dehydrogenase exists in multiple forms in mammalian tissues. The dimeric form of the enzyme has a primary structure distinct from previously known mammalian enzymes and may constitute a novel protein family with prokaryotic proteins. L-Xylulose ....Structural studies of mammalian dimeric dihydrodiol dehydrogenase and L-xylulose reductase. The aim of the research is determine the structures and mechanisms of mammalian dimeric dihrodiol dehydrogenase and L-xylulose reductase. Mammalian dihydrodiol dehydrogenase exists in multiple forms in mammalian tissues. The dimeric form of the enzyme has a primary structure distinct from previously known mammalian enzymes and may constitute a novel protein family with prokaryotic proteins. L-Xylulose reductase is an enzyme of the uronate cycle that accounts for about 5% of the total glucose metabolism per day in humans. We propose to determine the first structure of a L-xylulose reductase.Read moreRead less
Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomen ....Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomenon of ?potentiation? may serve to amplify signal-induced changes in the transcriptome at the translational level. This project will begin to unravel the molecular mechanisms underlying potentiation using experiments designed to distinguish between transcription- and translation-driven mechanisms.Read moreRead less
INTRINSIC PROPERTIES OF THE PORE FORMING DOMAIN OF THE RYANODINE RECEPTOR CALCIUM CHANNEL. The project is to understand how a calcium ion channel is able to regulate muscle performance. The ion channel, known as the ryanodine receptor, is essential for human and animal survival. The results of the project will be integral to understanding muscle performance in humans and will have long term implications for Australian sports physiology and sports science. The project will also be integral to ....INTRINSIC PROPERTIES OF THE PORE FORMING DOMAIN OF THE RYANODINE RECEPTOR CALCIUM CHANNEL. The project is to understand how a calcium ion channel is able to regulate muscle performance. The ion channel, known as the ryanodine receptor, is essential for human and animal survival. The results of the project will be integral to understanding muscle performance in humans and will have long term implications for Australian sports physiology and sports science. The project will also be integral to understanding muscle performance and development in animals and will have repercussions for the Australian livestock and racing industries. The results may lead to the development of new insecticides since insect mobility depends on ryanodine receptor activity. This will benefit to Australian agriculture.Read moreRead less
Studies on the stereospecific interaction between aldose reductase and inhibitor. There is no therapy specific for treatment of diabetes complications accepted worldwide. The enzyme aldose reductase has shown promising results as a drug target for preventing or delaying the onset of the complications. The structures of human aldose reductase holoenzyme in complex with stereoisomers of the potent inhibitor Fidarestat will be determined at high resolution in order to elucidate the binding modes re ....Studies on the stereospecific interaction between aldose reductase and inhibitor. There is no therapy specific for treatment of diabetes complications accepted worldwide. The enzyme aldose reductase has shown promising results as a drug target for preventing or delaying the onset of the complications. The structures of human aldose reductase holoenzyme in complex with stereoisomers of the potent inhibitor Fidarestat will be determined at high resolution in order to elucidate the binding modes responsible for the differences in their inhibitory potencies. The results may lead to the design of better inhibitors of the enzyme for the treatment of diabetes sufferers, at least until better methods for maintaining metabolic control are developed.Read moreRead less
Structure-based discovery of dipeptidyl peptidase IV inhibitors. Diabetes afflicts approximately 151 million people worldwide, with an estimated increase to 221 million by 2010. To date, no therapy for the treatment of diabetes complications is widely accepted. The enzyme dipeptidyl peptidase IV has shown promising results as a target for the treatment of type 2 diabetes. Structural studies of dipeptidyl peptidase IV in complex with inhibitor will be conducted to elucidate the details of the e ....Structure-based discovery of dipeptidyl peptidase IV inhibitors. Diabetes afflicts approximately 151 million people worldwide, with an estimated increase to 221 million by 2010. To date, no therapy for the treatment of diabetes complications is widely accepted. The enzyme dipeptidyl peptidase IV has shown promising results as a target for the treatment of type 2 diabetes. Structural studies of dipeptidyl peptidase IV in complex with inhibitor will be conducted to elucidate the details of the enzyme-inhibitor interaction. The results will be used to identify the molecular basis of potency and selectivity of dipeptidyl peptidase IV inhibitors and may lead to the discovery of pharmaceutical agents for the treatment of diabetes sufferers.Read moreRead less
Crystallographic studies of aldose and aldehyde reductases. The ability of aldose reductase to reduce the excess glucose that results from the hyperglycaemia of diabetes has been linked to the development of diabetic complications. Recent studies link the lack of a clinically suitable aldose reductase inhibitor to lack of inhibitor selectivity. The structures of the complexes of aldose and aldehyde reductases with various inhibitors should allow us to establish the important aspects of the inh ....Crystallographic studies of aldose and aldehyde reductases. The ability of aldose reductase to reduce the excess glucose that results from the hyperglycaemia of diabetes has been linked to the development of diabetic complications. Recent studies link the lack of a clinically suitable aldose reductase inhibitor to lack of inhibitor selectivity. The structures of the complexes of aldose and aldehyde reductases with various inhibitors should allow us to establish the important aspects of the inhibitor interaction with the residues of the active site. This information will be used in the design of more specific aldose reductase inhibitors.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
Interfacial interactions with hydrogel biomaterials. The interactions between cells of the body and the surfaces of medical implants are controlled largely by the molecules that are adsorbed on the surface. The aim of this project is to evaluate the effect of modifying hydrogel biomaterials on the interactions of the molecules with the hydrogel. This, in turn, allows us to determine the factors affecting the control of the cell's response. The significance of this work is in the improved ability ....Interfacial interactions with hydrogel biomaterials. The interactions between cells of the body and the surfaces of medical implants are controlled largely by the molecules that are adsorbed on the surface. The aim of this project is to evaluate the effect of modifying hydrogel biomaterials on the interactions of the molecules with the hydrogel. This, in turn, allows us to determine the factors affecting the control of the cell's response. The significance of this work is in the improved ability to control cellular responses to implants. Such improved response will result in better health outcomes for patients, and outcomes in the form of papers and intellectual property.
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