CAREER: Imaging dynamic macromolecules in solution with x-ray lasers

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An award is made to Arizona State University (ASU) for the development of new biomolecular imaging techniques that exploit the unique capabilities of ultrabright x-ray sources. The research aims to enable broadly applicable methods of visualizing dynamic motions of proteins and other biomolecules in solution at physiological temperature. The education plan integrates undergraduate and PhD students into the specific research project, as well as the broader initiative to develop ultrafast x-ray science at ASU. Opportunities are tailored to undergraduate first-generation community college transfer students to engage in mentored independent research at ASU. A team of undergraduate and PhD students will work together toward complementary research goals and will travel to large-scale laboratory facilities, such as the Linac Coherent Light Source at SLAC National lab, to learn how diverse teams of scientists work together. Student career development will be supported through cross-training opportunities at collaborator institutes, participation in international conferences, assistance with individual development plans, and other forms of mentorship. A new freely available open-source software suite will be developed as a pedagogical tool to help a broader audience of students master x-ray data analysis methods and explore new imaging concepts. A complementary optical diffractive imaging laboratory apparatus will be developed to teach experimental techniques. These hardware and software tools will be integrated into undergraduate physics curriculum at ASU and will also provide a foundation for an interactive diffractive x-ray imaging display to be showcased at public outreach events at ASU. The educational plans are highly synergistic with the existing NSF BioXFEL Science and Technology Center and the Compact X-Ray Light Source facility at ASU’s Biodesign Institute.The scientific research targets the general need for measurement techniques that can reveal detailed three- dimensional structures and functional dynamics of biomolecules such as proteins. It develops x-ray scattering methods to determine structures without the need to grow macroscopic protein crystals or to cryogenically freeze samples, both of which are requirements of existing techniques that can limit their effectiveness for dynamic molecules. X-ray free-electron lasers are used to produce snapshot scattering patterns by outrunning atomic motions with intense ultrashort x-ray pulses of just 10 femtoseconds (10-14 seconds). Unlike conventional x-ray solution scattering, the analysis of two-point intensity correlations amongst snapshot scattering patterns can directly yield three-dimensional structures, and in favorable cases allows for chemically selective imaging of atomic sub-structures embedded in complex environments. Structural changes may be sequenced in time to form “molecular movies” by delaying snapshots until shortly after reactions are triggered with light flashes, temperature jumps, or by other mechanisms. These methods are applicable to a broad variety of biomolecular systems which includes, among numerous examples, proteins that are involved in photosynthesis, vision, viral infection, and signaling processes that regulate nearly all vital processes in living cells and organisms. Model protein systems studied in the course of this research will elucidate ultrafast dynamics of light-activated protein motions. In addition to the publication of results in peer-reviewed journals and presentations at scientific conferences, x-ray scattering data and analysis software will be made publicly available and will contribute to the general development of ultrafast x-ray imaging science. Similarly, innovative hardware technologies developed in the course of the research, such as micro-nozzle designs for the production of liquid nanodroplets, will be made publicly available.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.