Edward H. Snell, Ph.D.
Hauptman-Woodward Institute - Research Scientist
Assistant Professor of Structural Biology, SUNY-Buffalo

EDUCATION
B.Sc(Hons)1st, Applied Physics, John Moore University of Liverpool, 1992
Ph.D., Chemistry Department, University of Manchester, UK, 1996

MAILING ADDRESS:
Hauptman-Woodward
Medical Research Institute
700 Ellicott Street
Buffalo , NY 14203-1102

Research Interests

1. Radiation damage in X-ray crystallography
2. Free radical scavengers and metalloproteins
3. The development and use of neutron diffraction
4. Macromolecular crystal quality

1. Radiation damage in X-ray Crystallography

Radiation damage occurs when X-rays interact with matter in the crystal or mother liquor surrounding the crystal. Free radicals are formed which can migrate damaging the short-range and eventually long-range order of the crystal.  To some extent this damage can be mitigated by cryocooling.  Our aims are three fold;

• To understand radiation damage and identify the fingerprints of the process.
• To mitigate the damage through improved cryocooling techniques and the use of radiation product scavengers.
• To make use of controlled radiation damage for structural mechanism studies.

Studies to understand radiation damage center round a model protein, xylose isomerase. Xylose isomerase has an active site that is very sensitive to the damage.  Starting from data at 0.95Å resolution we have gradually incurred damage through successive data sets reducing the overall resolution to 1.20Å. The radiation causes defined structural changes in the enzyme.

X-ray and thermal imaging camera studies are being used to investigate cryoprotectants (McFerrin and Snell, 1999) and the cryocooling process itself (Snell et al., 2002).

2. Free radical scavengers and metalloproteins

We are currently developing Extracellular SOD (ecSOD) as a crystallization target along with Fibulin-5/DANCE, a binding protein for ecSOD. Understanding the structure and mechanism of these proteins is important in understanding many common cardiovascular diseases. We are also in the early stages of studies on P450's important in drug metabolism.

3. The development and use of neutron diffraction

Neutron diffraction does not cause radiation damage and is unique in its ability to detect deuterium at resolutions of approximately 2Å. This means, by the replacement of hydrogen with deuterium, one can determine key hydrogen positions, protonation state and study samples and physiologically relevant temperatures.

Neutron flux is weak and hence neutron diffraction has not been developed as a well used technique. However, with the use of the Laue method studies have been increasing at sources in the US, France and Japan. The Spallation Neutron Source at Oak Ridge, Tennessee is under construction and will greatly increase the available neutron flux enabling many experiments that are currently not possible. We are working on the other side of the problem by increasing crystal volume with a number of model proteins and targets for our own structural studies.

4. Macromolecular Crystal Quality

There are many ways of judging a good crystal. For the structural crystallographer, the primary desideratum is the concept of internal order. 

Quality in a crystal can be described as long-range or short-range.  In general long-range disorder in the crystal gives rise to localized effects in reciprocal space and vice versa.  For example, crystal mosaicity, which is a large-scale property in real space, causes the localized effect of broadened spots in reciprocal space whereas the effect of random disorder between adjacent unit cells is a global, resolution-dependent reduction in diffracted intensity in reciprocal space. Thus, careful measurements of the diffraction from macromolecular crystals can reveal the degree and nature of their disorder.  Since macromolecular crystals are, by the standard of small molecule crystals, not very good crystals, they offer a fruitful field for the study of disorder.  A better understanding of the nature and causes of disorder in macromolecular crystals can lead to the production of better crystals.