Dynamic Force Microscopy of small molecular assemblies. The possibility of manipulating a single molecule seems at first unreal, indeed 5 years ago it was pure science fiction. Through the gaining popularity of the Atomic Force Microscope (AFM) many perspectives about the molecular world are changing. Macroscopic effects such as adhesion and lubrication are now discussed in light of measurements made with this instrument. Newer work includes the observation of single protein unfolding experim ....Dynamic Force Microscopy of small molecular assemblies. The possibility of manipulating a single molecule seems at first unreal, indeed 5 years ago it was pure science fiction. Through the gaining popularity of the Atomic Force Microscope (AFM) many perspectives about the molecular world are changing. Macroscopic effects such as adhesion and lubrication are now discussed in light of measurements made with this instrument. Newer work includes the observation of single protein unfolding experiments. The biophysics oriented project detailed in this application will extend the AFM: into multi-molecular systems formed by self-assembly, such as cell membranes; into polyelectrolyte-surface interactions; and, finally into the sequencing of DNA.Read moreRead less
Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation r ....Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less
Mechanisms and consequences of myeloperoxidase-mediated damage to glycosaminoglycans, proteins and proteoglycans. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in we ....Mechanisms and consequences of myeloperoxidase-mediated damage to glycosaminoglycans, proteins and proteoglycans. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.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
Biochemistry of tropoelastin and elastin: the molecular architecture of elastic fibre assembly. Elastin destruction drives the progression of emphysema, a major component of chronic obstructive pulmonary disease which is a major cause of death. Loss of elastin leads to profound blockage of arteries. If we are to treat these problems we need to know how to make and repair elastin. This research will enable us to discover how elastin is constructed and define its interacting partners. We will lear ....Biochemistry of tropoelastin and elastin: the molecular architecture of elastic fibre assembly. Elastin destruction drives the progression of emphysema, a major component of chronic obstructive pulmonary disease which is a major cause of death. Loss of elastin leads to profound blockage of arteries. If we are to treat these problems we need to know how to make and repair elastin. This research will enable us to discover how elastin is constructed and define its interacting partners. We will learn how to make tissue components found in parts of the body that expand and contract such as the arteries, lung and skin. We will learn about the molecular mechanisms of elastin assembly and cell interactions, which gives us the core molecular toolkit to repair elastin tissue.Read moreRead less
The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the rece ....The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the receptor to block immunological responses, contributes to chronic illness states. At this point we have good evidence that anandamides are immunoregulators, however, we have very little knowledge of their precise physiological role. The aim of this research is to begin to characterise the immunoregulatory role of the anandamide system. This project will provide a comprehensive understanding of this endogenous control system, the immunological properties of which have not previously been described. The outcome of this research may lead to the identification of new avenues for the development of pharmaceutical interventions that can target this system.Read moreRead less
Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosph ....Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosphate ester bonds in biological molecules will be developed. Active complexes will be incorporated into nanosized peptide nucleic acid (PNA) - metal complex hybrids and applied as artificial enzymes in the sequence specific cleavage of RNA and DNA. Novel applications of these ?artificial enzymes? in biotechnology are anticipated.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775590
Funder
Australian Research Council
Funding Amount
$200,000.00
Summary
A single crystal X-ray diffractometer with CCD detector for structural analysis of small molecules. In recent years their have been major advances in the capacity of instrumentation to determine the crystal and molecular structure of chemical compounds and materials which in turn has resulted in a rapidly growing understanding of the relationship between the structure of molecules and their function in the design of new materials and as drugs for the treatment of disease and pain. This infrastr ....A single crystal X-ray diffractometer with CCD detector for structural analysis of small molecules. In recent years their have been major advances in the capacity of instrumentation to determine the crystal and molecular structure of chemical compounds and materials which in turn has resulted in a rapidly growing understanding of the relationship between the structure of molecules and their function in the design of new materials and as drugs for the treatment of disease and pain. This infrastructure also provides training of an international standard for undergraduate and post graduate students, thus building the skills capabilities of Australian scientists in the workforce.Read moreRead less
Chemistry of the Transport of Nutrient Copper in Biological Cells. Nutrient trace metals such as copper are needed for enzymes by living organisms but are toxic in excess. Defects in copper metabolism cause Menkes and Wilson diseases in humans and there are direct connections to neurodegenerative diseases (eg, Alzheimer, Parkinson, Creutzfeldt-Jakob, motor neuron diseases). It is crucial to understand how healthy cells control toxic but essential copper so that enlightened intervention is possib ....Chemistry of the Transport of Nutrient Copper in Biological Cells. Nutrient trace metals such as copper are needed for enzymes by living organisms but are toxic in excess. Defects in copper metabolism cause Menkes and Wilson diseases in humans and there are direct connections to neurodegenerative diseases (eg, Alzheimer, Parkinson, Creutzfeldt-Jakob, motor neuron diseases). It is crucial to understand how healthy cells control toxic but essential copper so that enlightened intervention is possible when disturbances of copper metabolism become pathological. The chemistry of key molecules will be studied to reveal their essential properties and thereby to understand the molecular basis of the copper-linked diseases.Read moreRead less
Molecular Characterisation of Metal Transport Proteins. The trace metals are essential to life. The secrets of their catalytic and structural roles are under intensive scrutiny. The molecular mechanisms which regulate concentrations of nutrient metals in biological cells remain poorly understood. Errors in metal metabolism cause disease. For example, defects in copper metabolism cause Menkes and Wilson diseases in humans and there are connections of copper and zinc to neuro-degenerative disea ....Molecular Characterisation of Metal Transport Proteins. The trace metals are essential to life. The secrets of their catalytic and structural roles are under intensive scrutiny. The molecular mechanisms which regulate concentrations of nutrient metals in biological cells remain poorly understood. Errors in metal metabolism cause disease. For example, defects in copper metabolism cause Menkes and Wilson diseases in humans and there are connections of copper and zinc to neuro-degenerative diseases such as Alzheimer and Creutzfeldt-Jakob (mad cow). This project will study the chemistry of metabolic pathways responsible for import of nutrient copper and other metals into biological cells.Read moreRead less