Robert Thorne

Professor, Stephen H. Weiss Presidential Fellow

Summary

My interests include single-particle cryo-electron microscopy and X-ray diffraction studies of protein structure and dynamics; the physics of water, ice, and aqueous glasses; biological cryopreservation; X-ray fluorescence imaging of ancient artifacts; charge-density-wave conductors; and physics education.

Research Focus

 

Single-Particle Cryoelectron Microscopy of Biomolecules

Advances in direct electron detectors, microscope phase plates, and analysis software in the last decade have transformed single-particle cryo-electron microscopy (cryoEM) into a workhorse tool for determining near-atomic-resolution structures of large biomolecules and their complexes.  We are focused on unraveling physical phenomena in sample preparation, cryocooling, and sample interaction with electron beams that limit achievable resolution and on developing methods for time-resolved cryo-EM of biomolecular function. 

X-ray Diffraction Studies of Biomolecular Structure and Dynamics

Atomic-resolution structures of proteins and other biological macromolecules determined using X-ray crystallography provide insight into molecular function and the basis for design and discovery of new pharmaceutical compounds.  We are focused on developing methods to increase both the quality and kinds of information about protein structure, energy landscapes, and function that can be obtained via crystallography. Most recently, we have demonstrated a new and powerful approach for making “molecular movies” with millisecond resolution of biomolecules in action and are developing instrumentation to make this approach routine.  Several of our discoveries have been commercialized by MiTeGen, LLC, and are used by structural biologists around the world.

Small Angle X-Ray Scattering of Biomolecules at Cryogenic Temperature

Small-angle X-ray scattering (SAXS) is a simple and powerful technique for extracting low-resolution information about biomolecular structure and changes in structure in response to, e.g., drug binding and temperature changes. We have made the first successful SAXS measurements on biomolecules at cryogenic temperatures. We are working to develop cryoSAXS into a general-purpose method that dramatically reduces sample volumes and data collection time per measurement and to facilitate high-throughput screening of, e.g., potential pharmaceutical compounds.

Ice Nucleation, Growth, and Glass Formation in Aqueous Systems

The remarkably complex phase diagram of water and the physics of ice nucleation and growth are important in fields ranging from cryobiology and cryopreservation to cloud formation and climate change. We have studied fundamental aspects of ice and glass formation in aqueous systems, especially in nanoconfined bio-environments, and their application in cryoEM, cryoSAXS, and cryocrystallography of biomolecules. We are currently collaborating with Cornell’s College of Veterinary Medicine in studies of ice formation and associated cellular damage mechanisms to identify in cryopreservation of oocytes and and embryos for assisted reproduction.

X-ray Fluorescence Imaging of Ancient Artifacts

In collaboration with classicists and archaeologists, we have used synchrotron-based X-ray fluorescence imaging and complementary methods to study ancient artifacts including Greek and Latin inscriptions on stone, ancient glasses from Iraq, and artifacts from the Maya and other Mesoamerican cultures.  XRF imaging allows us to explore the tools and materials used in creating the objects, to discover how the objects looked at the time of their creation, and to recover lost or hidden text and images.

Physics Education

Future U.S. economic competitiveness depends upon our ability to recruit and train a highly skilled workforce in science, technology, engineering, and the health professions.  Physics is a critical gateway to all of these disciplines, and provides the foundation for fundamental understanding, for analyzing data, and for solving problems. Following Cornell’s long tradition of innovation in physics education, I have developed teaching methods and materials that engage students of diverse backgrounds and interests, and that help them to develop both mastery of and a broader appreciation for physics. With two high school physics teachers (Marty Alderman and Jim Overhiser) I established our Undergraduate Teaching Assistant program in 2008 and ran it through 2018.  The program introduces roughly 100 Cornell undergraduates per semester to the practical and intellectual challenges of teaching in our introductory physics courses, and provides support for our honors physics courses through the 3000 level. I redeveloped and teach Physics 4484/7684 “Teaching and Learning Physics”.  This course discusses big ideas in teaching and learning, gives nuts and bolts training to deal with challenges in the classroom and beyond, and develops a leadership mindset.    

Postdoctoral Associates
Jonathan Clinger
Matthew McLeod

Undergraduate Students
Alkis Boukis
Andrew DiFabbio

I have openings for two postdoctoral associates, two graduate students and two undergraduates. 

Publications

Millisecond mix-and-quench crystallography (MMQX) enables time-resolved studies of PEPCK with remote data collection.  J. A. Clinger, D. W. Moreau, M. J. McLeod, T. Holyoak, and R. E. Thorne. IUCrJ 8, 784-792 (2021). DOI: 10.1107/S2052252521007053

High-resolution single-particle cryo-EM of samples vitrified in boiling nitrogen.  T. Engstrom, J. A. Clinger, K. A. Spoth, O. B. Clarke, R. Jayne, B. A. Apker and R. E. Thorne.  IUCrJ 8, 867-877 (2021). DOI: 10.1107/S2052252521008095

Integrated sample handling and mounting system for fixed-target serial synchrotron crystallography.  G. Illava, R. Jayne, A. D. Finke, D. Closs, W. Zeng, S. K. Milano, Q. Huang, I. Kriksunov, P. Sidorenko, F. W. Wise, W. R. Zipfel, B. A. Apker and R. E. Thorne.  Acta Cryst. D 77, 628-644 (2021). DOI: 10.1107/S2059798321001868.

Hypothesis for a mechanism of beam-induced motion in cryo-electron microcopy.  R. E. Thorne. IUCrJ 7, 416-421 (2020). DOI: 10.1107/S2052252520002560.

Resolution and dose dependence of radiation damage in biomolecular systems. H. Atakisi, L. Conger, D. W. Moreau, and R. E. Thorne. IUCrJ 6, 1040-1053 (2019).  DOI: 10.1107/S2052252519008777

Solvent flows, conformation changes and lattice reordering in a cold protein crystal. D. W. Moreau, H. Atakisi and R. E. Thorne.  Acta Cryst. D 75, 980-994 (2019). DOI: 10.1107/S2059798319013822

Ice formation and solvent nanoconfinement in protein crystals. D. W. Moreau, H. Atakisi, and R. E. Thorne.  IUCrJ 6, 346-356 (2019).  DOI: 10.1107/S2052252519001878

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams.  M. A. Warkentin, H. Atakisi, J. B. Hopkins, D. Walko, and R. E. Thorne, IUCrJ 4, 785-794 (2017).  DOI: 10.1107/S2052252517013495

Mapping the Conformational Landscape of a Dynamic Enzyme by XFEL and Multitemperature Crystallography. D. A. Keedy, L. R. Kenner, M. Warkentin, J. B. Hopkins, R. A. Woldeyes, M. C. Thompson, A. S. Brewster, A. H. Van Benschoten, E. L. Baxter, M. Uervirojnangkoorn, J. M. Holton, W. I. Weis, A. T. Brunger, S. M. Soltis, H. Lemke, A. Gonzalez, N. K. Sauter, A. E. Cohen, H. van den Bedem, R. E. Thorne and J. S. Fraser. Elife 4, e07574 (2015). DOI: 10.7554/eLife/07574

Breaking the radiation damage limit with cryo-SAXS. S. P. Meisburger, M. Warkentin, H. Chen, J. B. Hopkins, R. E. Gillilan, L. Pollack and R. E. Thorne. Biophys. J. 104, 227-236 (2013). DOI: 10.1016/j.bpj.2012.11.3817

Application of X-ray fluorescence imaging to ceramics from the American Southwest. E. C. Geil, S. A. LeBlanc, D. S. Dale and R. E. Thorne. J. Arch. Sci. 40, 4780-4784 (2013). DOI: 10.1016/j.jas.2013.05.014

Critical droplet theory explains the glass formability of aqueous solutions. M. Warkentin, J. P. Sethna and R. E. Thorne. Phys. Rev. Lett. 110, 015703 (2013). DOI: 10.1103/PhysRevLett.110.015703

X-ray fluorescence recovers writing from ancient inscriptions.  J. Powers, N. Dimitrova, R. Huang, D. M. Smilgies, D. H. Bilderback, K. Clinton, and R. E. Thorne. Zeitschrift fur Papyrologie und Epigraphik 152, 221 (2005).

Growth and disorder of macromolecular crystals: insights from atomic force microscopy and X-ray diffraction studies. A. J. Malkin and R. E. Thorne. Methods 34, 273 (2004). DOI: 10.1016/j.ymeth.2004.03.020

Charge-density-wave conductors. R. E. Thorne. Physics Today. May 1996, p. 42. DOI: 10.1063/1.881498

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