Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develo ....Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develop innovative methods to investigate, and importantly modulate, DNA and RNA triple helix assembly, specificity and molecular interactions. Resulting insights will underpin novel approaches to gene regulation, principally in the context of designing new antibacterial agents to address the antibacterial resistance problem.Read moreRead less
Pluses and minuses of lipid mass spectrometry. This project aims to investigate the structural diversity of lipids. Lipids are among the most structurally diverse of all the biomolecules and thus deciphering their many functions requires bio-analytical technologies capable of uniquely identifying and quantifying individual molecules in a milieu of many thousands of analogues. Mass spectrometry is the pre-eminent technique for contemporary lipid analysis but is challenged by the preference of cer ....Pluses and minuses of lipid mass spectrometry. This project aims to investigate the structural diversity of lipids. Lipids are among the most structurally diverse of all the biomolecules and thus deciphering their many functions requires bio-analytical technologies capable of uniquely identifying and quantifying individual molecules in a milieu of many thousands of analogues. Mass spectrometry is the pre-eminent technique for contemporary lipid analysis but is challenged by the preference of certain lipids to ionise with a polarity that affords sensitive detection but does not permit detailed structure elucidation. This project will develop advanced instrumentation capable of on-demand polarity switching of ionised lipids such that the detection and interrogation of molecular structure can take place in the optimal charge state.Read moreRead less
Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid ....Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid separation, identification and quantification of isomeric lipids. These next generation technologies will be deployed in the hope of unmasking the molecular diversity within the lipidomes of two important mammalian cell types, thus providing fundamental new insights into the structure and function of lipids within living systems.Read moreRead less
Developing the basis for an quality control platform for human pluripotent stem cells and their differentiated derivatives. Biophotonic techniques based on spectroscopy have the potential to provide low-cost, automatable measurements for the quality control of stem and differentiated cells produced for use in industry and regenerative medicine. This project is aimed at acquiring the fundamental scientific knowledge base required to bring this about.
The photons take charge: Elucidating the structure and stability of distonic radical anions by mass spectrometry and photoelectron spectroscopy. Recent work has discovered that certain radical anions have electronic configurations that defy chemical convention and exhibit exceptional radical stability. Exploitation of this breakthrough first requires experimental elucidation of the intrinsic electronic structure of these compounds and how it relates to their remarkable properties. This project w ....The photons take charge: Elucidating the structure and stability of distonic radical anions by mass spectrometry and photoelectron spectroscopy. Recent work has discovered that certain radical anions have electronic configurations that defy chemical convention and exhibit exceptional radical stability. Exploitation of this breakthrough first requires experimental elucidation of the intrinsic electronic structure of these compounds and how it relates to their remarkable properties. This project will probe the fundamental structure and energetics of radical anions by modifying instrumentation to enable multi-step gas-phase ion synthesis to be efficiently coupled with anion photoelectron spectroscopy. These investigations are essential to revealing the scope of this phenomenon in free radical chemistry and biology and could inform future development of new catalysts for polymerisation.Read moreRead less
New laser and mass spectrometry-based tools for comprehensive structural elucidation of lipids and their biomolecular interactions. Lipid-related disorders such as obesity, diabetes and heart disease are reaching epidemic proportions. We propose the development of specialised instrumentation to identify and quantify lipids (fats) in tissue and culture samples thus providing Australian scientists with unique capabilities to investigate the mechanisms of disease.
Synthesis and Characterisation of Encoded Hybrid Polymer/Gold Nanoparticles for Application in Bioassays. Bioassays are the cornerstone of in vitro diagnostic and biomedical research. This proposal will significantly contribute to these areas, by targeting an emerging technology that is crucial for their future development. The hybrid nanoparticles described in this project have the potential to replace conventional detection strategies that are currently used for bioassays. In doing so, they sh ....Synthesis and Characterisation of Encoded Hybrid Polymer/Gold Nanoparticles for Application in Bioassays. Bioassays are the cornerstone of in vitro diagnostic and biomedical research. This proposal will significantly contribute to these areas, by targeting an emerging technology that is crucial for their future development. The hybrid nanoparticles described in this project have the potential to replace conventional detection strategies that are currently used for bioassays. In doing so, they should provide significant advantages over conventional detection strategies. These advantages include increased sample throughput and conservation of biological samples, which makes possible the acceleration of patient diagnosis and drug discovery. Read moreRead less
Estimating Time Since Death: Application of Radionuclide Technology. This study will
- advance the knowledge base and expertise of Australian anthropologists and forensic scientists through the development of an accurate method for determining time since death from skeletal remains
- directly assist police and forensic forces in their fight against crime, which is fundamental in ensuring the national security of Australia
- promote Australia as a leader in the design of new evidence-bas ....Estimating Time Since Death: Application of Radionuclide Technology. This study will
- advance the knowledge base and expertise of Australian anthropologists and forensic scientists through the development of an accurate method for determining time since death from skeletal remains
- directly assist police and forensic forces in their fight against crime, which is fundamental in ensuring the national security of Australia
- promote Australia as a leader in the design of new evidence-based forensic methods
- raise the profile of Australian scientists in international investigations involving skeletal remains (e.g. Bali bombing, Boxing Day Tsunami, Human Rights Issues)
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Pushing the Boundaries of Multi-modal Biospectroscopic Microscopies. In order to understand the fundamentals of life processes, diseases, and their treatments, it is essential to probe fundamental changes in molecular processes in cells, tissues and whole organisms. Much of our understanding of these processes has involved the introduction of chemical probes for biospectroscopy, but these have inherent problems because the probe can often change the biochemistry that is being probed. This projec ....Pushing the Boundaries of Multi-modal Biospectroscopic Microscopies. In order to understand the fundamentals of life processes, diseases, and their treatments, it is essential to probe fundamental changes in molecular processes in cells, tissues and whole organisms. Much of our understanding of these processes has involved the introduction of chemical probes for biospectroscopy, but these have inherent problems because the probe can often change the biochemistry that is being probed. This project will push the boundaries of a variety of micro and nano "probe-free" microscopies to provide fundamental insights into these life processes, which could ultimately lead to improvements in the diagnosis, prevention and treatment of diseases.Read moreRead less
Mass spectrometry to reveal the role of lipids in protein misfolding. This project aims to develop an integrated mass spectrometry-based approach to determine structures and dynamics of membrane associated proteins, and discover how lipids cause protein misfolding implicated in neurodegeneration. Lipid membranes may influence protein (mis)folding, aggregation and related toxicity. However, the complex and dynamic nature of the lipid-protein interactions involved means traditional methods cannot ....Mass spectrometry to reveal the role of lipids in protein misfolding. This project aims to develop an integrated mass spectrometry-based approach to determine structures and dynamics of membrane associated proteins, and discover how lipids cause protein misfolding implicated in neurodegeneration. Lipid membranes may influence protein (mis)folding, aggregation and related toxicity. However, the complex and dynamic nature of the lipid-protein interactions involved means traditional methods cannot easily characterise them, and they are poorly understood at a molecular level. The project expects to develop tools to bridge a critical gap in structural biology, while understanding lipid-protein interactions could lead to new therapies. This will ultimately provide benefits such as reduced health costs and better health outcomes.Read moreRead less