Trapped Ion Imaging for Biomolecular Dynamics. The functionality of large biological molecules is driven by their chemical composition and the folded shape of their active form. The higher-order structure and dynamics of nucleic acids, proteins, carbohydrates, and lipids drives the chemistry of life. Combining single molecule microscopy and trapped ion mass spectroscopy will develop a new tool for precision measurements of higher-order folding dynamics in large biomolecules. Optical techniques i ....Trapped Ion Imaging for Biomolecular Dynamics. The functionality of large biological molecules is driven by their chemical composition and the folded shape of their active form. The higher-order structure and dynamics of nucleic acids, proteins, carbohydrates, and lipids drives the chemistry of life. Combining single molecule microscopy and trapped ion mass spectroscopy will develop a new tool for precision measurements of higher-order folding dynamics in large biomolecules. Optical techniques including Förster resonance energy transfer and super-resolution imaging can register changes in shape down to the nanometer scale. The uniquely adaptable ion trap environment enables manipulation of the surrounding solvent cage, temperature, and net charge down to the single quantum level. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100624
Funder
Australian Research Council
Funding Amount
$372,529.00
Summary
The impact of structural dynamics on three-dimensional bioimaging with X-ray free-electron lasers. X-ray lasers can potentially determine the structures of biological molecules that are inaccessible to existing techniques. Intense ultrafast pulses encode the structure via diffraction faster than damage processes rip the molecule apart. In fact, damage processes begin during diffraction and remain problematic. It is not known if damage will prevent the determination of molecular orientations, a c ....The impact of structural dynamics on three-dimensional bioimaging with X-ray free-electron lasers. X-ray lasers can potentially determine the structures of biological molecules that are inaccessible to existing techniques. Intense ultrafast pulses encode the structure via diffraction faster than damage processes rip the molecule apart. In fact, damage processes begin during diffraction and remain problematic. It is not known if damage will prevent the determination of molecular orientations, a critical step in the experimental design. This project will solve this problem with a statistical theory, probing the feasibility and accuracy of the technique. The newly developed theory will enable us to perform experiments capable of measuring the effects of damage in biological molecules, paving the way for new methods of structure determination.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101061
Funder
Australian Research Council
Funding Amount
$424,848.00
Summary
Single particle imaging: x-ray imaging of individual dynamic biomolecules. X-ray lasers produce powerful ultra-short pulses of light that can take temporal snap shots of small radiation-sensitive biological complexes. Thanks to superconducting technology, the next generation of x-ray lasers will be able to produce x-ray pulses at greater rates than ever before. But because of the sheer number of possible molecular configurations, these molecular movies will have only a small amount of data per f ....Single particle imaging: x-ray imaging of individual dynamic biomolecules. X-ray lasers produce powerful ultra-short pulses of light that can take temporal snap shots of small radiation-sensitive biological complexes. Thanks to superconducting technology, the next generation of x-ray lasers will be able to produce x-ray pulses at greater rates than ever before. But because of the sheer number of possible molecular configurations, these molecular movies will have only a small amount of data per frame, posing an enormous challenge for current imaging methods. I aim to meet this challenge by developing an innovative multi-conformational image reconstruction algorithm. This will provide a new window into the molecular dynamics of biological systems, the building blocks of life, and enable rational drug design.Read moreRead less