Paul Adams, Head of the Berkeley Center for Structural Biology
As a Deputy Division Director in the Physical Biosciences Division I lead the Berkeley Center for Structural Biology (BCSB), which provides five macromolecular crystallography (MX) beamlines for a very broad user community. Two of the beamlines (8.2.1 and 8.2.2) are funded by the Howard Hughes Medical Institute (HHMI). The other three beamlines (5.0.1, 5.0.2 and 5.0.3) are funded by a number of industrial and academic users, with a significant contribution from the National Institutes of Health. The sector 8.2 beamlines use one of the 5T superbend sources that provide x-rays in the 5-16keV range. The tunability of the x-rays is essential for many of the experiments performed by macromolecular crystallographers, and is one of the reasons that synchrotron sources have become so popular in this field.
The three sector 5.0 beamlines share a common 1.96T, 56 pole, 11.5cm period, permanent magnet wiggler source from which 5.0.2 accepts the central 1.5mrad of the emission fan and 5.0.1 and 5.0.3 each accept a 2.7mrad wide sidefan. The central beamline, 5.0.2, is a fully-tunable beamline with an energy range of 4-16keV. The two sidestations are monochromatic but have an x-ray energy that has been chosen to exploit the anomalous scattering of X-rays by many biologically important elements (in particular selenium).
Researchers use the BCSB beamlines to obtain very high-resolution images of biomolecules, such as enzymes, viruses, and DNA. The majority of the structures are important for improving human health, by designing better therapeutics or understanding how diseases occur. The crystallographic technique relies on growing very uniform crystals of purified biomolecules and then using diffraction methods to obtain the distribution of electrons in the crystal. This enables an atomic model to be constructed and interpreted.
Outside of the BCSB, I lead a research group that develops software for automated macromolecular crystallography: a program called Phenix used by researchers around the world to analyze the diffraction data collected at MX beamlines. I also have research projects, looking at protein folding and developing new biofuels, which use the BCSB beamlines to solve structures.
The BCSB consists of several beamline scientists (Simon Morton, Corie Ralston, and Peter Zwart), a software development group (led by John Taylor), and a number of technical and administrative staff. They maintain the beamlines so that they can be used by researchers from around the world, and they develop the beamlines’ capabilities.
In the last five years we have performed major upgrades of the sector 5.0 beamlines to increase x-ray flux by 10- to 30-fold. On sector 8.2 we have started an upgrade of beamline optics that will eventually result in a 10-fold increase in beam brightness, taking advantage of the ALS top-off and sextapole magnet upgrades.
All of the BCSB beamlines now have robotic hardware for the handling of crystals. This has made it possible to provide remote access to the beamlines so that many of the users now collect data from their home institutions instead of travelling to Berkeley. We also provide a Collaborative Crystallography Program, led by Banu Sankaran, where users send crystals for data collection and structure solution (see the ALSNews feature Solving Structures with Collaborative Crystallography to learn more about this program).
We are now looking at how to further develop the BCSB beamlines, focusing on the possible introduction of a super-cooled insertion device on sector 5.0 to provide a very high-brightness, low-divergence beam.
We are fortunate at the ALS to have a community of structural biology beamlines. There are three other macromolecular crystallography beamlines: 4.2.2, 8.3.1, and 12.3.1. The latter beamline is unique in providing both crystallography and small angle X-ray scattering techniques. There are also unique resources at the ALS for tomographic imaging of biological systems: the National Center for X-Ray Tomography, and the use of infrared spectroscopy at the Berkeley Synchrotron Infrared Structural Biology Program. Collectively, these structural biology resources are essential to research in the Physical Biosciences, Life Sciences, and Earth Sciences Divisions. In the near future I will be establishing a Biosciences Council to foster interactions between these groups and with the ALS.