At next-generation synchrotron light sources, tiny, powerful x-ray beams -
especially of sub-micron size - could substantially advance research in
several areas of structural biology, particularly macromolecular crystallography
(MX). Such was the consensus of the approximately 100 participants at the "MX
Frontiers at the One Micron Scale" workshop held at BNL
on July 23 and 24. Workshop talks also illuminated the benefits that micro-beams
will offer for the mitigation of radiation damage; however, all agreed that
more experimental verification and method development is needed.
Participants at the 2009 MX Frontiers Workshop
The workshop was particularly relevant given the development of National Synchrotron
Light Source II (NSLS-II), a brilliant new synchrotron facility under construction
at BNL. The unusually substantial list of interested sponsors for the workshop
included the NSLS-II Project, BNL's National Synchrotron Light Source
(NSLS), the Office of Biological & Environmental Research and the Office
of Basic Energy Sciences in the DOE Office of Science, Brookhaven Science Associates,
BNL's Biology Department, the National Institutes of Health's National
Center for Research Resources, and the National Institute of General Medical
Sciences. Commercial support was provided by FMB-Oxford Ltd, Bruker ASC, and
Area Detector Systems Corporation.
As he welcomed participants on the first morning of the workshop, Laboratory
Director Sam Aronson highlighted the essential role played by the crystallography
community at the NSLS and expressed his hopes for their continued involvement
in leveraging the expanded capabilities of NSLS-II. During the workshop, organized
by BNL's Dieter Schneider, Marc Allaire, and Lonny Berman, speakers on
the first day lectured about scientific opportunities, new crystallographic
methods, radiation damage, and micro-focusing beamlines. The next day was devoted
to beamline concepts and challenges in optics and instrumentation. Posters were
displayed on both days for viewing and discussion during coffee and lunch breaks.
Aptly, the workshop allowed speakers and participants to weigh in on how recent
developments in crystallography may be used to inform the design of beamlines
at NSLS-II. Workshop speakers and participants underscored the importance of
incorporating full-automation and beamlines with the flexibility to deliver
a stable one micron beam as well as larger beams. Regarding the future at NSLS-II,
Wayne Hendrickson, NSLS-II Associate Project Director for Life Sciences, predicted
that "what we think of as difficult today will become routine by 2015."
David Eisenberg of UCLA illustrated just this development by discussing his
adventures in micro-crystallography that led to the discovery of the mis-folded
state of amyloid peptides that cause Alzheimer's and related diseases.
He anticipates that increasingly brilliant x-ray beams and continued advances
in micro-techniques will eventually allow him to investigate amyloid crystallites
in vivo, inside intact cells. Christian Riekel, his longtime collaborator and
a pioneer in microdiffraction, expanded these views and outlined the ideas that
he and his colleagues apply in advancing from micro- to nano-diffraction methods.
In addition to considering new ideas for NSLS-II, some speakers shared current
developments and future plans for other synchrotron facilities, including the
Advanced Photon Source at Argonne National Laboratory, the European Synchrotron
Radiation Facility (ESRF) in Grenoble, France, the Swiss Light Source in Switzerland,
the Diamond Light Source in England, and SPring-8 facility in Japan. By bringing
together scientists from such widespread facilities, the workshop also provided
a unique opportunity in scientific community building.
"To address issues that will come up in the next five to 10 years, we
need to find better ways to integrate and share access to beamlines,"
said Sean McSweeney of ESRF, emphasizing the value of cooperative development.
Likewise, Gebhard Schertler, MRC Laboratory of Molecular Biology, Cambridge,
UK, indicated, "It is important how beamline scientists work with other
scientists - they have to work on equal terms."
The workshop concluded with a final discussion considering the key question
of whether or not a solid case had been made in favor of micro-beams. Participants
debated the matter with enthusiasm throughout, deliberating the appropriateness
of the one-micron scale, the role of sub-micron beams, and the usefulness of
beamlines with flexible capabilities.
Although as Colin Nave of Diamond pointed out, "We're not yet in
the position where all the possibilities have been explored."
Ultimately, the sum of lectures and discussions clearly illustrated that tiny
beams will enable new science, particularly so if the beam is of sub-micron
size. At this scale, structural work will be characterized by experimentation
rather than routine measurements and involve many pursuits in life sciences
such as MX, small-angle x-ray scattering, and fiber diffraction, and potentially
borrowing from electron microscopy. Finally, the workshop illuminated the benefits
that micro-beams offer for the mitigation of radiation damage, but that more
experiments must be done and methodologies developed to ensure that micro-beams
are used to their best advantage.