The Snell Laboratory


Dr. Edward Snell, a Fellow of the American Crystallographic Association (the Structural Science Society), is a biophysicist who led the Hauptman-Woodward Medical Research Institute as Chief Executive Officer and president for 9 years. He is the Chief Scientific Officer at the Institute and has over 90 publications, four book chapters, and two books. He serves on numerous advisory committees. The Snell Group is engaged in methods development that leads to a deeper understanding of biological structure, function, and mechanism. The laboratory is predominantly interested in crystallography with an ever-increasing focus on complementary techniques to extend and enhance the understanding of dynamics on top of the structure. Ongoing projects include the enhancement of high-throughput crystallization processes, accurate interpretation of metalloprotein structure, and specific structural projects related to cancer therapy and treatment. Dr. Snell is also the Director of the NSF BioXFEL Science and Technology Center, an effort to develop the biological applications of X-ray Free Electron Lasers.

See the Snell Laboratory personal website at

Laboratory News

Some of the structures the laboratory has been involved with

Research in the Snell Laboatory

Current focus

Our current research focus is in the study of the structural impacts of X-ray radiation at therapeutic doses and understanding a range of biological systems that are involved in free-radical based biological processes. This is reflected in a number of our recent publications developing a sensitive measure of residue-specific radiation chemistry at doses of a few Grey, looking at the dynamics of systems thought to be triggered by free radical driven processes, and the accurate metal determination in metalloproteins. All provide the tools and techniques for the study of medically important systems that are linked to free radical processes.

Our research builds on a history of developments in crystallization, the use of SAXS, precious radiation chemistry studies, and methods to optimize and make use of the physical quality of protein crystals. We are extending our expertise to cryo-electron microscopy and spectroscopic methods.  Publications related to our current and historical focus areas are provided at the bottom of the page.

Crystallization research

We have developed methods to make high-throughput become high-output. We have aimed to decrease the steps involved in going from an initial crystallization hit to a diffraction pattern through several developments. The first of these is in defining a means to optimize crystallization conditions using only the chemicals causing the initial hit. A simple drop volume ratio coupled with temperature variation allows the closet space to the nucleation and metastable region in the phase diagram to be traversed. If there is not enough sample to replicate or optimize a hit a novel means to reproducibly extract and mount the crystal as devised. Very simply, using the transparent properties of the plate observation could occur opposite to the extraction. A capillary can remove the crystal and deposit it into a loop. In situ methods have superseded this approach but they will be a topic of a later citation. Historically we can learn a lot, successful approaches in the past will be successful in the future. Coupling this with the knowledge that many crystals appear before we can observe them microscopically and the methods that we can use to observe them at these stages is useful knowledge in exploring and understanding fundamental crystal growth. These developments are made available to the community from our screening laboratory.

Development and use of SAXS

We have made use of complementary techniques to explain the difference between tRNA synthesis in prokaryotes and eukaryotes. Small-angle X-ray scattering (SAXS) resolution was poor and the results ambiguous. With the advent of modern detectors, improved beams, and the computational power to run mathematically intense algorithms SAXS has changed. The combination of SAXS, crystallography, and molecular dynamics was used to explain the differences in eukaryotic and prokaryotic tRNA synthesis, specifically the role of appended domains in eukaryotic systems. In doing so we have established the fidelity of SAXS as a technique and developed high-throughput methods to characterize a sample and determine if there are different oligomeric states in solution and crystal. In doing so we established quality criteria for SAXS data that distinguishes between data that can be treated routinely by standard software from that needing an expert analysis and finally data that is not usable. This opens up a previously subjective analysis for the use of SAXS by a much wider audience and enables its complementary application with other structural techniques.

Radiation chemistry impact on the structure

We developed a physical model of disulfide bond damage from irradiation based on studies on cryocooling and using a combination of crystallography, spectroscopy, and electron paramagnetic resonance. We determined that cryocooling causes a cold wave to flow through the crystal cooling it from the side nearest the cold source to the side furthest from it establishing a gradient across the crystal. Gradients in d-spacing are therefore continuous along the crystal axis. A microbeam would see good data in all points with a gradual increase in cell parameters as a function of distance from the cold source. The beam itself heats the sample. This can be considerable, taking it where OH radicals are immobilized to above this point with detrimental consequences for structural data. Maintaining an air stream to remove heat has a dramatic effect on this process and is a requirement to minimize beam heating even at ambient temperatures. The cooling itself can be reversible using large amounts of cryoprotectants to promote annealing success. Our data shows that disulfide bonds are radicalized in the first image. We discovered an unexpected damage repair process, such that with a sufficient dose rate, the damage that occurs before useful diffraction stops can be reduced.

The physical quality of protein crystals

Probing long-range order in crystallization shows that protein crystals have similar if not better physical characteristics to solid-state crystals. Solid-state physics has used X-ray techniques to characterize crystals for a long time. During the 1990s crystals were being grown in space to use the reduced convection properties of freefall to minimize convection over the crystal surface. Applying rocking width measurements to crystals we found that mosaicity was greatly reduced in a reduced convection growth environment. Unfortunately, mosaicity is a long-range effect while resolution depends on short-range order – diffraction resolution is not enhanced. Topography and reciprocal space mapping confirmed the result and also pointed the way to a means to exploit long-range order for a higher signal to noise, i.e. fine slicing or continuous rotation data collection. This is now possible. Interestingly the physical quality of macromolecular crystals studied at physiological temperatures can be so good that an explicit treatment of diffraction may be needed rather than the kinematical approximation used currently.

Publications by year (over 90 total) (click here).








  • Double-flow focused liquid injector for efficient serial femtosecond crystallography. Oberthuer D, Knoška J, Wiedorn MO, Beyerlein KR, Bushnell DA, Kovaleva EG, Heymann M, Gumprecht L, Kirian RA, Barty A, Mariani V, Tolstikova A, Adriano L, Awel S, Barthelmess M, Dörner K, Xavier PL, Yefanov O, James DR, Nelson G, Wang D, Calvey G, Chen Y, Schmidt A, Szczepek M, Frielingsdorf S, Lenz O, Snell E, Robinson PJ, Šarler B, Belšak G, Maček M, Wilde F, Aquila A, Boutet S, Liang M, Hunter MS, Scheerer P, Lipscomb JD, Weierstall U, Kornberg RD, Spence JC, Pollack L, Chapman HN, Bajt S.  Sci Rep. 2017 Mar 16;7:44628.
  • Moving in the Right Direction: Protein Vibrational Steering Function. Niessen KA, Xu M, Paciaroni A, Orecchini A, Snell EH, Markelz AG.  Biophys J. 2017;112:933-942.






















  • Lysozyme crystal growth kinetics monitored using a Mach-Zehnder interferometer. Snell EH, Helliwell JR, Boggon TJ, Lautenschlager P, Potthast L. Acta Crystallogr D Biol Crystallogr. 1996 May 1;52(Pt 3):529-33.
  • An Investigation of the perfection of lysozyme protein crystals grown in microgravity and on earth. Helliwell, JR, Snell, EH, & Weisgerber, S. Springer Lecture notes in Physics. Vol 464, Ch. 30 edited by Ratke, L., Walter, H. & Feuerbache, B. Springer Verlag, 155-170 (1996).
  • X-ray topography: An old technique with a new application. Stojanoff, V, Siddons, DP, Snell, EH and Helliwell, JR. Synchrotron Radiation News 9, 25-26 (1996).
  • Trends and challenges in experimental macromolecular crystallography. Chayen NE, Boggon TJ, Cassetta A, Deacon A, Gleichmann T, Habash J, Harrop SJ, Helliwell JR, Nieh YP, Peterson MR, Raftery J, Snell EH, Hädener A, Niemann AC, Siddons DP, Stojanoff V, Thompson AW, Ursby T, Wulff M. Q Rev Biophys. 1996.



  • Electron density maps of lysozyme calculated using synchrotron Laue data comprising singles and deconvoluted multiples.  Campbell , JW, deacon, A, Habash, J, Helliwell, JR, McSweeney, S, Quan, H, Raftery, J and Snell, E. Bull. Mater. Sci., 17,1, 1-18 (1994).


  • The emergence of the synchrotron Laue method for rapid data collection from protein crystals. Cassetta, A, Deacon, A, Emmerich, C, Habash, J, Helliwell, JR, McSweeney, S, Snell, E, Thompson, AW and Weisgerber, S.  Proc. R. Soc. Lond. A, 177-192 (1993).


  • John Moores University of Liverpool, UK, Physics, B.Sc. Hons (1st) – 1992.
  • University of Manchester, UK, Chemistry, Ph.D. – 1996.
  • NASA Biophysics Laboratory, Marshall Space Flight Center, USA, National Research Council Fellow.