Shear stimulated Brillouin microscopy for cell mechanobiology. This project aims to develop novel technology for non-contact imaging of micro-mechanical properties in cells and tissues to answer fundamental questions of cell mechnanobiology. Based on principles of Brillouin light scattering, the project takes advantage of a radio-frequency lock-in detection scheme. The project will result in a real-time, high-sensitivity, non-contact 3D imaging solution for spatial characterisation of cell's loc ....Shear stimulated Brillouin microscopy for cell mechanobiology. This project aims to develop novel technology for non-contact imaging of micro-mechanical properties in cells and tissues to answer fundamental questions of cell mechnanobiology. Based on principles of Brillouin light scattering, the project takes advantage of a radio-frequency lock-in detection scheme. The project will result in a real-time, high-sensitivity, non-contact 3D imaging solution for spatial characterisation of cell's local stiffness and compressibility. This will underpin the advancement of knowledge in the area of cell mechanobiology and the investigation of diseases, where microscale changes in cell mechanical properties lead to cell dysfunction and apoptosis.Read moreRead less
Elucidating the mechanisms by which Scribble, Discs Large and Lethal Giant Larvae regulate epithelial polarity. Discs Large (Dlg) and Scribble are proteins that regulate cell shape by concentrating at particular regions within the cell and recruiting other proteins to that region. It is thought that the two proteins interact with each other, and with other proteins involved in protein trafficking and cell architecture, but it is not known how these events coordinate to produce a net outcome on ....Elucidating the mechanisms by which Scribble, Discs Large and Lethal Giant Larvae regulate epithelial polarity. Discs Large (Dlg) and Scribble are proteins that regulate cell shape by concentrating at particular regions within the cell and recruiting other proteins to that region. It is thought that the two proteins interact with each other, and with other proteins involved in protein trafficking and cell architecture, but it is not known how these events coordinate to produce a net outcome on cell shape. To answer these questions, the dynamic events involved in localization of Dlg, Scribble, and associated proteins will be determined, in mammalian cells and in whole organs of the vinegar fly.Read moreRead less
Connecting the dots: Image analysis for single molecule localisation microscopy. It is now possible to record the positions of single fluorescent molecules in intact cells to build up an image literally molecule by molecule. But how to ‘connect the dots’ and extract structural information from molecular coordinates is yet to be worked out. The project aims to do exactly that, and write and implement novel analysis routines to quantify a diverse range of biological structures such as protein comp ....Connecting the dots: Image analysis for single molecule localisation microscopy. It is now possible to record the positions of single fluorescent molecules in intact cells to build up an image literally molecule by molecule. But how to ‘connect the dots’ and extract structural information from molecular coordinates is yet to be worked out. The project aims to do exactly that, and write and implement novel analysis routines to quantify a diverse range of biological structures such as protein complexes, membrane morphologies, filamentous cytoskeletal networks, vesicles and viruses. The project is a collaboration between a cell biologist (Professor Gaus) who is a leader in single molecule localisation microscopy, an expert in fluorescence image analysis (Dr Nicovich) and an industry partner (Dr Lucas) who has a sophisticated software platform.Read moreRead less
Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nan ....Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nanotechnology would therefore benefit from this work by basing their designs on the principles behind the mechanism of the bacterial motor. This research is also of interest for veterinary science, as motility by flagellar motor is a key virulence factor of common animal pathogens associated with, for example, listeriosis and gastroenteritis.Read moreRead less
Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are c ....Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are controlled, which is vital for developing better treatments for neurological disorders such as stroke. The project will also provide research training in experimental/computational molecular biology, which is a rapidly growing field underpinning the biotechnological and pharmaceutical industries. Read moreRead less
Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales ....Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales with molecular dynamics at small distances and shorter times. Applications to both membrane proteins (blocking of ion channels by toxins and drugs) and globular proteins (ligand binding to receptors and protein association) will be considered.Read moreRead less
Structure and function of the protein translocation channels in the mitochondrial outer membrane. Biological membranes are the basis of life and understanding how proteins are inserted into membranes is a major goal in the Biological Sciences. The TOM complex is a molecular machine mediating protein insertion into a biological membrane. Recent successes with X-ray diffraction of protein crystals, and solution and solid-state NMR spectroscopy have heralded leaps-and-bound advances for our knowled ....Structure and function of the protein translocation channels in the mitochondrial outer membrane. Biological membranes are the basis of life and understanding how proteins are inserted into membranes is a major goal in the Biological Sciences. The TOM complex is a molecular machine mediating protein insertion into a biological membrane. Recent successes with X-ray diffraction of protein crystals, and solution and solid-state NMR spectroscopy have heralded leaps-and-bound advances for our knowledge of how membranes work at the molecular level. Using a combination of phylogenetic analysis, yeast genetics and these new techniques from structural biology, we will characterize the structure and function of the core from the TOM complex.Read moreRead less
Ultrahigh resolution crystallography and ultrafast laser spectroscopy to uncover the evolution and mechanisms of a unique algal light harvesting system. The results of our research will provide the first comprehensive understanding of a biological light harvesting system at high temporal, energetic and spatial resolution. This will allow us to understand how nature has evolved highly efficient strategies for trapping light. The benefits of this work include spawning ideas as to how to improve ....Ultrahigh resolution crystallography and ultrafast laser spectroscopy to uncover the evolution and mechanisms of a unique algal light harvesting system. The results of our research will provide the first comprehensive understanding of a biological light harvesting system at high temporal, energetic and spatial resolution. This will allow us to understand how nature has evolved highly efficient strategies for trapping light. The benefits of this work include spawning ideas as to how to improve current technologies for enhancing optoelectronic devices and solar collectors. Protein systems are by nature nanotechnology. The understanding gained through probing a natural nanosystem will enhance our understanding of how human designed nanophotonic systems will behave. Read moreRead less
Functional Dissection of the Bacterial Replisome. We now have the complete sequences of genes in humans and many other organisms, but we know much less about how the protein products of the genes communicate with each other to create and grow cells. Australia has recently invested heavily in state-of-the-art instruments that can be used to tackle these problems. This project will involve close interaction of four laboratories to use new instruments to determine how a large assembly of proteins i ....Functional Dissection of the Bacterial Replisome. We now have the complete sequences of genes in humans and many other organisms, but we know much less about how the protein products of the genes communicate with each other to create and grow cells. Australia has recently invested heavily in state-of-the-art instruments that can be used to tackle these problems. This project will involve close interaction of four laboratories to use new instruments to determine how a large assembly of proteins interact in a biological machine that makes DNA. This process occurs in similar ways in all organisms, and is essential for life. Understanding how DNA is made will help scientists to develop new antibacterial drugs, and learn how to make practical use of molecular machines that imitate biology.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882855
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
High-resolution imaging of live cells and tissue. Understanding the machinery of life and developing technologies that support life's processes requires biological and physical scientists and engineers to monitor molecular events in living systems. The aim is to take advantage of very recent developments in light microscopy to enable the non-invasive imaging of live cells and tissue at a previously unreachable level of detail. The instruments will form the nucleus of a new imaging facility. Sign ....High-resolution imaging of live cells and tissue. Understanding the machinery of life and developing technologies that support life's processes requires biological and physical scientists and engineers to monitor molecular events in living systems. The aim is to take advantage of very recent developments in light microscopy to enable the non-invasive imaging of live cells and tissue at a previously unreachable level of detail. The instruments will form the nucleus of a new imaging facility. Significant advances in research areas including vascular research, cancer, immunology, cell and molecular biology, functional genomics, biotechnology, nanotechnology and material engineering will be of major benefit both nationally and globally.Read moreRead less