Edward H. Snell,
Chief Executive Officer
Assistant Professor of Structural Biology, SUNY-Buffalo
B.Sc(Hons)1st, Applied Physics, John Moore
University of Liverpool, 1992
Ph.D., Chemistry Department, University of Manchester, UK, 1996
Crystallography is the dominant technique for visualizing biological macromolecules at the atomic level, and the existence of high-quality crystals is a key requirement for successful crystallographic experiments. However, the growth of such crystals is often a major obstacle. Therefore, one of the major goals of my laboratory is to develop greater understanding of the crystallization process and to improve the methodology for elucidating the structure, function and dynamics of large biological molecules. Complementary techniques are also being developed for use when crystallization is not successful or to add additional information to the crystallographic structure. My research falls into four related areas: crystallization, solution scattering techniques, understanding the effect of the technique on the structure, and making use of the methodology developed to obtain new biological information.
My laboratory is situated adjacent to the Hauptman-Woodward Institute’s high-throughput crystallization screening laboratory, which is directed by Joseph Luft and is one of the largest laboratories of this type in the world. The two labs work together to develop practical approaches for initial crystallization screening (PMID 25005076), to examine different methods of evaluating experimental outcome (PMID 25084371), and to make use of the crystals that result (PMID: 24904250). The high-throughput laboratory has a vast archive of data from 15 years of crystallization screening experiments, and we are actively involved in developing means to use that information for predictive crystallization strategies (PMID: 24971458). We are also collaborating with other groups that have similar interests (PMID: 24988076).
2. Small Angle X-ray Scattering
More often than not, crystallization attempts initially fail or samples remain recalcitrant to crystallization. Even if crystallization experiments are successful, dynamics in the structure may not be resolved. In cases like these where satisfactory crystallographic work is not possible, I use the complementary solution scattering technique known as Small-Angle X-ray Scattering (SAXS). My colleagues and I have developed methods for evaluating the quality of SAXS data and validated their use by comparing previously known structures to SAXS results (PMID: 21462184). We are actively developing algorithms and techniques to enhance the use of SAXS for driving crystallization experiments, characterizing samples, and potentially extending the information that can be derived.
3. Radiation Damage
My research team is experienced in using X-ray sources for crystallographic experiments in the home laboratory, at synchrotron radiation sources, and at X-ray laser sources. Radiation damages biological specimens, and we are is examining the effects of this damage on the results of structural studies (PMID: 24311579).
4. New Biological Information
The ultimate goal of methods development is to elucidate new structural information. I am combining complementary methods that lead to more accurate structural information and have multiple collaborations in this area. For example, we have made use of neutron scattering to study enzymes (PMID: 24531475), of SAXS as a tool to validate basic shape information (PMID: 23383235), and of Nuclear Magnetic Resonance (NMR) in combination with computational modeling to understand structure. Of particular importance is the combination of crystallography, SAXS, and molecular dynamics to provide structural and mechanistic information (PMID: 23583912; PMID: 22180531).