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
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
Correlative Imaging of Brain Lipids. This project aims to develop imaging tools and protocols for the detection of lipids in brain tissue and cells. This project expects to generate advanced methodologies to display specific lipid classes and their corresponding structures within tissues and cells, with the ability to be detected and correlated with multiple techniques, which represent a currently unavailable capacity. The expected outcomes of this project are improved opportunities to study lip ....Correlative Imaging of Brain Lipids. This project aims to develop imaging tools and protocols for the detection of lipids in brain tissue and cells. This project expects to generate advanced methodologies to display specific lipid classes and their corresponding structures within tissues and cells, with the ability to be detected and correlated with multiple techniques, which represent a currently unavailable capacity. The expected outcomes of this project are improved opportunities to study lipid biology at the cellular and sub-cellular level across a wide range of in vitro and in vivo models. The outcomes of this project should provide significant knowledge to tackle modern societal challenges in healthy ageing, brain pathologies and neurodegenerative diseases.Read moreRead less