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[an error occurred while processing this directive] Report from the 2006 Meeting of the American Crystallographic Association

By Jeremy M Kowalczyk, SPS Reporter, University of Hawaii

2006 ACA Meeting  
The 2006 Meeting of the American Crystallographic Association (ACA) was held July 22-27, 2006 in Honolulu, Hawaii.  

Being a physics graduate student primarily interested in nanoscience and optics, and without much knowledge of crystallography, I wasn’t sure how much I would get out of attending the 2006 Meeting of the American Crystallographic Association (ACA).  Of course it was held in Honolulu, Hawaii, where I happen to be going to graduate school, so at least it wasn’t a huge expense.  The first question I was asked at the opening reception, "are you small molecule or large molecule?", and my complete lack of understanding of it did not bolster my confidence of learning anything.  Fortunately, I was able to understand a lot in the sessions and learn from a group of experienced and friendly scientists.

Crystallography, (literally the study of crystals) is most commonly done today by striking a sample crystal of a substance with an unknown structure with x-rays.  X-rays are scattered by the electron clouds of a particular atom or molecule.  A photon is absorbed by an electron, it moves into a higher energy state, and eventually decays back to the ground state, emitting a scattered photon.  The way in which this scattering process occurs is dependent on the electronic structure of the atom or molecule, so information on the structure and constituents of the target can be ascertained from the scattering pattern produced by many incident photons.  When I think of crystals, I envision something like NaCl or some other very regular, natural crystal.  However, most of work done today is on large molecular samples, supramolecules (large molecules composed of smaller submolecules each of which performs a specific task), and proteins. Proteins in solution that are made into a crystal by using a diffusion gradient or by concentration though controlled evaporation.  Although great strides have been made in improving crystallization experiments, crystal creation, particularly for membrane proteins, is still quite a challenging aspect of crystallography today.

2006 ACA Meeting  
SPS Reporter Jeremy Kowalczyk (right) with Judith Kelly (left) at the opening reception of the 2006 Meeting of the ACA.  

Before the opening reception, I had a chance to speak with the ACA program chair, Judith Kelly.  Judy is an emeritus professor at the University of Connecticut studying protein structure and function using x-ray diffraction.  She has been an ACA member for over 30 years.  Looking at the session titles, it was easy to see why she had been selected as the program chair.  Structural Biology in Industry, BioMacromolecular Assemblies, Structural Genomics-Big and Small, and Membrane Protein Structures were just a few of the sessions that dealt with the determination of protein structure.  When I asked her about what is hot in crystallography, she mentioned three things: nanotechnology, macromolecular crystallography, and neutron diffraction.  There is a push in the industry to study larger molecules, which tend to be harder to prepare and analyze.  Also, the use of neutrons instead of x-rays is becoming more prolific as new technology is becoming available (more on that later).

Judy was excited by the Undergraduate Research Showcase session that was scheduled.  She said not only does a research experience help participating students hone their research skills, but it also helps them find which areas of expertise they like or dislike before choosing a graduate program.  As advice to undergraduates, she said this: "Get involved, go to seminars, and talk to your professors!  They want to talk to students who are excited about their research."

Armed with a better feel for crystallography and some of the hot topics, I dove into the sessions.  The first one I attended was Grazing Incidence Methods for Nanoscience and Biotechnology.  D.I. Svergun discussed how the grazing-incidence small-angle x-ray spectroscopy (GISAXS) detector at the Argonne Advanced Photon Source (APS) allow for scientists to now look at molecular and atomic reactions as they are happening.  In one example, he showed how as a crystal grew layer by layer, one can see how the 1-D hexagonal lattice of the first couple layers transitions into a body centered cubic (BCC) structure.  Different layers of the material can be viewed by increasing the grazing angle at which the x-rays are incident, causing them to diffract off increasingly deeper layers of the material.  The precision of the GISAXS is such that the structure of each individual layer can be resolved.

The next talk focused on nanoparticles and how grazing incidence techniques allow one to look at how they assemble at interfaces such as that between water and a virus.  This has the possible application of using nanoparticles to deliver medicine to eliminate viruses or destroy cancerous cells.  Another talk focused on how GISAXS allows a scientist to closely monitor the growth of nanoparticles which allows for very tight control over the their size.  Nanoparticles are used in a wide array of applications from band gap tuning of semiconductor devices to the purification of water.

2006 ACA Meeting  
Left to right: Gregory Ferrence, Kazuo Katagiri, Meg Fasulo, Katherine Kantardjieff, Marilyn Olmstead in front of Diamond Head and Waikiki.  

In the afternoon, I attended the Undergraduate Research Showcase.  It started off with a talk by Katherine Kantardjieff on the state of education in crystallography.  While she stated that she has seen more interest in crystallography by students at California State University Fullerton (where she is a professor) over the past few years, generally there are fewer people going into the field and it is becoming more rare to find it in the curriculum before graduate school.  According to surveys conducted by the United States National Committee for Cystallography, the introduction to crystallography that has typically been found in physical chemistry texts has been removed in the newest editions.  This causes less exposure and consequently less interest in the field by new students.  Even the students who do become interested end up studying crystallography for a comparatively short amount of time, leading to a deficient knowledge of the field.

Many biology and chemistry students that use crystallographic analysis end up treating it as a "black-box".  They put their samples in and take the results from the computer as golden.  If they understood the process of crystallography: how x-rays diffract off different atoms and how to analyze the patterns generated, they would be better equipped to deal with incorrectly modeled structures which arise from today’s software.  The audience of about 40 people resonated with this.  Some complained that they have seen this lack of understanding in their graduate students and even some professional crystallographers.  Gregory Ferrence (presenter of the next talk) even commented that his students have caught obviously incorrect structures in professional crystallographic publications.   

To address these problems, Katherine and her colleagues are proposing inclusion of crystallography in more texts even down to the junior high level.  They have already seen newest releases of introductory chemistry texts including crystallography, so it looks like things are moving in the right direction.

This led nicely into a talk by Illinois State University’s Gregory Ferrence which dealt with remote access to crystallographic analysis.  Through a network of schools that have remotely accessible x-ray diffraction instrumentation, students in locations without such hardware can use these machines.  The students prepare crystal samples and send them to the remote location.  Once the samples are in place, the remote users can control the experiment and analysis through the internet.  This allows for more students to access the necessary tools and have an authentic research experience in crystallography; leading to a larger group of well trained crystallographers in the future.

2006 ACA Meeting  
Poster Session.  

Next there were two talks by undergraduates.  Meg Fasulo of Kansas State University gave an impressive talk on co-crystals.  Co-crystallization is a method of changing the solubility and thermal stability of a particular substance, without changing its chemical action.  She gave pharmaceuticals as an application: a drug can be made shelf-stable and easily delivered to the body by making it into a co-crystal.  A hydrogen atom on one end of the drug is hydrogen bonded to a ligand (any molecule that binds to another).  She compared this to creating a salt out of the drug in question, where a hydrogen is replaced by a metal (or a radical that acts like a metal).  While creating a salt can also change solubility and thermal stability, in her study it changed the chemical effect in ~46% of the cases, while a co-crystal only changed the chemical effect in about 5% of the cases.  The talk focused on how to better create and identify co-crystals by using different ligands to form them.

Kazuo Katagiri of Boston College gave a very detailed analysis of a range of protein-ligand docking programs.  These programs help pharmaceutical companies see how a drug will dock itself on a host receptor or show molecular chemists how different ligands and proteins fit together.  Each program has its advantages for particular applications, and Kazuo explored which program is best for each.  Although both students were a little nervous, they both did an excellent job at doing some cutting-edge research, and they’re still undergraduates!

The next morning, I headed to the Transactions Symposium entitled The Future of Neutron Crystallography.  There, ACA President Robert Bau gave a talk on the basics of neutron crystallography and its future.  Neutrons interact with a molecular sample in a fundamentally different way than x-rays.  Neutrons are uncharged, so they do not interact via electromagnetic forces, but they have a spin of ½, so they have a spin interaction between other particles with spin.  The spin interaction is dependent on the magnitude of the spins of the two interacting particles, so a spin ½ nucleus will scatter a neutron in detectably different way than say a spin 2 nucleus.  This gives neutrons three primary advantages over x-rays:

  1. Location of light atoms: the electron cloud of light atoms like hydrogen have a small interaction cross section with x-rays, making identifying a hydrogen atom difficult.  However, the nucleus of light atoms like hydrogen have a relatively large interaction cross section with neutrons, making it easier to map them.
  2. Isotope discrimination: To x-rays a deuterium (2H) and a hydrogen (1H) atom look nearly identical since their electron clouds differ only slightly.  Since the deuterium atom nucleus has a spin of 1 and the hydrogen has a spin of ½, neutrons (which have a spin of ½) scatter differently off them, allowing for discrimination between the two.
  3. Magnetic structure determination: The interaction between spins and local magnetic fields of a sample allows a scientist to map its magnetic structure.  This is useful to discriminate ferromagnetic and antiferromagnetic materials, for instance.

Of course, these advantages come at a price.  I caught up with Robert Bau after the conference and told me about some of the disadvantages.

  1. Sources of neutrons are few and far between.  Typically, a nuclear reactor specifically tailored for neutron crystallography is required.  Spallation sources are another option.  Spallation occurs when a high-energy particle (typically a proton) hits a heavy nucleus such as mercury.  This causes the nucleus to become unstable and eventually decay into lighter atoms while ejecting 20-30 neutrons per event.  This allows for relatively high flux pulses of neutrons for crystallographic work. 
  2. The neutron flux from neutron sources is between 5 and 10 orders of magnitude less than x-ray sources.  This makes getting a sufficient number of scattering events more time consuming than in the x-ray case.
  3. >Crystals must be large:  Since neutron fluxes are low and interaction cross sections for neutrons with matter are small, a typical crystal must be large in order to increase the number of scattering events.  While crystals used with x-rays can be 0.1 mm3 or less, those used with neutrons typically need to be between 1 and 10 mm3.  This is the primary difficultly in neutron crystallography of proteins.  Growing such a large protein crystal of high quality is so difficult that neutron crystallography is often impractical.  

Still the advantages of neutrons make them a useful tool.  Just two years ago, scientists used neutron crystallography to correct the structure of Kevlar that had been incorrect for 30 years!  See Gardner, English, Forsyth, Macromolecules 37, 9654-9656 (2004) for details.

I also had time to attend the Synchrotron Special Interest Group (SIG) meeting.  Synchrotron radiation is an ideal source for x-ray crystallography.  The radiation is nearly monochromatic, high flux, has high and tunable energy, and small angular dispersion.  The only problem is you need a kilometer circumference synchrotron to get it!  The purpose of the meeting was to plan sessions for next year’s conference.  A very interesting device, the compact light source (CLS), came up as a topic for next year.  It is a miniature synchrotron light source with the footprint of a typical desk.  Soon crystallographers will be able to do analysis in their home labs instead of traveling to synchrotrons and waiting for beam time.

On the final day of the conference I attended the Metal-Organic Hybrids-Crystal Engineering session.  This class of materials has applications in photovoltaics and LEDs, where their processability, flexibility, lightweight, and low cost are highly advantageous.  You’ve probably already seen flexible video screens, which are based on organic LEDs.  Structures of metals and organic materials can be constructed such that the band gap of the material can be tuned to particular frequencies of light.  Jing Li of Rutgers University focused on changing the band gap of semiconductor materials by creating networks of semiconductor slabs and ligand interconnects.  By varying the slab thickness and dimensionality of the material, her group was able to show some tunability in the band gap.

After the conference was over, I had a chance to talk with Robert Bau, the ACA President. He gives a big Mahalo to the Sheraton Waikiki for being so accommodating to the conference attendees, especially the students.  Robert grew up in Hong Kong, but went to UCLA to do his Ph.D. in spectroscopy of organic-metallic structures.  Spectroscopy turned out to not be a good technique for determining these irregular structures, so Robert ended up learning crystallography from Mel Churchill of the State University of New York at Buffalo.  After that he was offered a postdoc position studying proteins with William N. Lipscomb, the 1976 Nobel Prize winner in chemistry, but declined and headed back to California, this time to University of Southern California, where he eventually became a professor.

According to Robert, there are a number of hot areas in crystallography today.  When I asked him about protein structure analysis he said "This is where the action is".  Between 50 and 60 percent of the attendees at the conference were doing protein crystallography.  The large flux of people into this realm has been spurred largely by the Human Genome Project and pharmaceutical companies.  Such entities are always trying to better understand proteins and their functions, and crystallography is the main way to do it.  All of this work has led to the creation of the Protein Data Bank, a world-wide database of all solved protein structures that is available to anyone.  When a scientist publishes a paper about a solved protein structure he/she is required to submit the structure to the database.  If the structure happens to be proprietary, the researcher has one year between when he/she publishes the results and when the structure must be included in the database for public access.  I though it was very encouraging to see such a collaborative effort in an industry where protein structures can be so lucrative.

With so much interest in protein structures, one would think that jobs are readily available for a protein crystallographer, but that doesn’t seem to be the case according to those I talked to.  I attended the Mentor/Mentee dinner during the conference and talked with many of the postdocs there.  The consensus was that job opportunities in the industry were few and the number of competing applicants high.  I asked Robert to comment on this, and he agreed that the market is close to saturated, although there are still opportunities for protein and macromolecular crystallographers, especially in the San Francisco and San Diego areas.  He gave the story of his own wife, Margaret Churchill, as evidence.  She was a molecular biologist  unable to find work for two years.  She finally became a patent agent and eventually a patent lawyer dealing with biology related patents.  Oddly enough, this was not an isolated case.  Robert said that two of his students at USC went on to become lawyers and now some schools such as the California Institute of Technology have started to offer law classes to their science students.  So despite the tightness of the market, there are still creative ways to keep working in a related field.

2006 ACA Meeting  
Left to right: SPS Reporter Jeremy Kowalczyk, Robert Bau, and Margaret Churchill at the Mentor/Mentee dinner.  

Looking back at the conference as a whole, I was impressed by the attitudes of most of the people I met.  Everyone was very enthusiastic and willing to explain their work, even in simple terms so that a non-biologist, non-chemist like me could understand.  Crystallography is an exciting field with a large variety of applications: protein structure, pharmaceuticals, photovoltaics, and nanostructures to name a few.  Attending the conference motivated me to learn some of the fundamental physics behind crystallography, quantum scattering, and learn more about nanostructures.  Conferences such as this are the best way I can think of to meet people, learn what is going on, and make connections for graduate school, postdocs, or employment in a particular field.  If I end up studying a field related to crystallography, I’ll be sure to attend next year’s conference in Salt Lake City.  Aloha and Mahalo for reading!

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