Multiphoton microscopy through tissue turbid media. The aim of this proposal is to conduct the collaborative project on multi-photon microscopic imaging through biological tissue, which has been recently initiated between Swinburne University of Technology (SUT) and Massachusetts Institute of Technology (MIT). It will integrate the special skills, two-photon fluorescence endoscopy and second-harmonic coherence tomography, investigated in the respective collaborating institutes, to develop a nove ....Multiphoton microscopy through tissue turbid media. The aim of this proposal is to conduct the collaborative project on multi-photon microscopic imaging through biological tissue, which has been recently initiated between Swinburne University of Technology (SUT) and Massachusetts Institute of Technology (MIT). It will integrate the special skills, two-photon fluorescence endoscopy and second-harmonic coherence tomography, investigated in the respective collaborating institutes, to develop a novel method for detecting/imaging cancer cells that are located at 1 mm below tissue surfaces, while they are still in the early stage to be cured. Consequently, a diagnostic method for early cancer detection particularly through skin tissue becomes possible.Read moreRead less
Diffractive Imaging using Soft X-rays and Electrons. Optical, electron and x-ray microscopy has yielded enormous biological insights and medical benefits to society. Optical microscopy is able to image live tissue, but at relatively low resolution. Electron microscopy can yield high resolution images, but only of highly prepared material. X-ray microscopy yields images of live tissue with a resolution that is intermediate between optical and electron microscopy. This project will provide Austral ....Diffractive Imaging using Soft X-rays and Electrons. Optical, electron and x-ray microscopy has yielded enormous biological insights and medical benefits to society. Optical microscopy is able to image live tissue, but at relatively low resolution. Electron microscopy can yield high resolution images, but only of highly prepared material. X-ray microscopy yields images of live tissue with a resolution that is intermediate between optical and electron microscopy. This project will provide Australian scientists with their first access to x-ray microscopy at its optimum wavelength; and secondly it will provide a superb testbed for x-ray microscopy to be enhanced using unique methods being developed in Australia.Read moreRead less
Nanometric optical sensing for characterisation of microbioreactors. Microfabrication of microfluidic based microbioreactors is a novel technology that is creating advanced tools in the fields of biology and medicine. A critically important step in the development of a microbioreactor is the ability to characterise fluid shear stress of the microenvironment without impacting on the biological system. The development of a microbioreactor in which individual or multiple cells can be cultured and ....Nanometric optical sensing for characterisation of microbioreactors. Microfabrication of microfluidic based microbioreactors is a novel technology that is creating advanced tools in the fields of biology and medicine. A critically important step in the development of a microbioreactor is the ability to characterise fluid shear stress of the microenvironment without impacting on the biological system. The development of a microbioreactor in which individual or multiple cells can be cultured and manipulated will have a significant impact on study of biological systems in cancer research and stem cell research. Read moreRead less
Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of ex ....Gas phase studies of the interactions of electrons with peptide ions: structure assignment and fundamentals. Electron-induced reactions are fundamental to a wide range of processes that underlie many areas of science and technology, ranging from planetary atmospheres, industrial plasmas to living tissues. Since ionizing radiation is believed to be a major cause of damage to living cells, understanding electron interactions with biological molecules is essential to predict the consequences of exposure. Structure determination of biomolecules is at the heart of identifying, diagnosing and potentially developing treatments for diseases, and thus another important reason for studying these interactions is the potential to develop new mass spectrometry based analytical methods.Read moreRead less
Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesi ....Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesis of inhibitors of these enzymes.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
Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to tr ....Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".Read moreRead less
Joint Theoretical and Experimental Electron Momentum Spectroscopic Studies for DNA Bases. The study of DNA structure is an area of intense research activity and continues to reveal new levels of complexity and diversity. Recent experiments (Science, 2002) provided direct evidences of the adenine non-planarity, indicating non-rigidity of DNA bases. Electron momentum spectroscopy (EMS) has been identified to be an appropriate technique in the study of chemical binding mechanism and orbitals at mol ....Joint Theoretical and Experimental Electron Momentum Spectroscopic Studies for DNA Bases. The study of DNA structure is an area of intense research activity and continues to reveal new levels of complexity and diversity. Recent experiments (Science, 2002) provided direct evidences of the adenine non-planarity, indicating non-rigidity of DNA bases. Electron momentum spectroscopy (EMS) has been identified to be an appropriate technique in the study of chemical binding mechanism and orbitals at molecular level. The aims of the project is to study orbitals and interactions of DNA and RNA bases such as adenine, thymine (uracil), guanine and cytosine using momentum space quantum mechanics and EMS experimental techniques. The outcome of the project will improve our understanding of the DNA double helical strand structure.Read moreRead less
Microcharacterisation of rare-earth-doped optical fibres. Rare-earth-doped optical fibres continue to play a central role in optical telecommunication systems and are increasingly being used as elements in optical fibre sensing devices and as fibre lasers. The aim of this project is the application of new high spatial resolution techniques for determining the physical properties of such fibres. These methods will permit unprecedented knowledge of the precise distribution of rare-earth ions in th ....Microcharacterisation of rare-earth-doped optical fibres. Rare-earth-doped optical fibres continue to play a central role in optical telecommunication systems and are increasingly being used as elements in optical fibre sensing devices and as fibre lasers. The aim of this project is the application of new high spatial resolution techniques for determining the physical properties of such fibres. These methods will permit unprecedented knowledge of the precise distribution of rare-earth ions in the fibre and its relationship with the fibre's refractive index profile. This information is critical to understanding the performance of rare-earth-doped fibres in a variety of applications and the outcomes of this work will inform the design of fibres optimised for use in specific applications.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