Berkeley Lab Gets NIH Grant for Second Generation of Automounter Robots

BERKELEY, CA — The first generation of automounter robots, machines that can automatically mount and align protein crystals in an x-ray beamline at a synchrotron light source, has been so successful that the National Institutes of Health (NIH) wants a second generation. NIH has awarded a three-year, $1.58 million grant to researchers at the Lawrence Berkeley National Laboratory (Berkeley Lab) to develop a new wave of robotic systems for high-throughput protein crystallography and related structural biology research.

(From left) James O'Neill, Thomas Earnest and Carl Cork with automounter 2, a second generation of robots that can automatically mount and align protein crystals in an x-ray beamline at a synchrotron light source.

"The next generation of automounter robots will offer enhanced capabilities of automated alignment, improved serviceability and robustness, and integrated machine vision capabilities," said Thomas Earnest, who leads the development of the robots. "We will also introduce sample tracking capabilities, featuring RFID chips."

Earnest is a biophysicist with Berkeley Lab's Physical Biosciences Division who leads the Structural Proteomics Development Group. He and his group developed the first generation of protein crystal automounter robots in collaboration with the bioinstrumentation group of Berkeley Lab’s Engineering Division. Members of these two divisions will again collaborate to develop the next-generation system.

With genome sequencing becoming almost a conveyer-belt process, one of the next big challenges in biology is to determine the structures of the proteins being assembled by all those genomes. Knowing the structural form of a protein is a key to understanding its molecular and cellular function. As there may be more than 30,000 different human proteins, and nearly a trillion different kinds of proteins on earth, solving protein structures is a process that screams out for automation.

The most widely used method today for determining protein structures is x-ray crystallography, in which a beam of x-rays is sent through a crystallized protein and scattered by the crystal’s atoms. This creates a diffraction pattern of dots that can be translated by computer into a 3-D model of the protein. When x-ray protein crystallography was done with low intensity beams from laboratory x-ray tubes, collecting complete diffraction data sets for a single protein crystal could take months or even years. All this changed with the arrival of synchrotron light sources which can generate x-ray beams that are on the order of a hundred million times more intense than the light from the most powerful x-ray tubes. Now, enough x-ray diffraction data for imaging a typical protein can be collected within an hour, or even, for some proteins, within minutes – providing you can quickly mount and align the protein crystals in the x-ray beamline.

Earnest and his colleagues scored a major achievement in February, 2001 when they introduced the first automounter robot to a protein crystallography beamline at Berkeley Lab’s Advanced Light Source. The ALS is an electron synchrotron and storage ring, designed to accelerate electrons to energies of nearly 2.0 billion electron volts (GeV) and extract from them – using either bending, wiggler, or undulator magnetic devices – premier beams of ultraviolet and x-ray light. A year later, a second and third robot were added, and these machines have helped make the ALS one of the premier facilities for x-ray protein crystallography in the world today.

"Speed is the big advantage of automation," said Earnest, who founded the ALS protein crystallography program with Sung-hou Kim, also of the Physical Biosciences Division, and ALS collaborators. "Whereas in the past it took about 15 minutes to manually mount and align a crystal, our automounter robots could perform the same task in less than three minutes. In the first five years of the robots' operation we were able to screen more than 10,000 protein crystals and collect complete structural datasets on several hundred of them."

The robot technology developed by Earnest and his colleagues proved so successful that researchers at other synchrotron light sources began collaborating with the Berkeley group toimplement the system. Today, automounter robots have been implemented at several beamlines at the Advanced Photon Source at Argonne National Laboratory, the National Synchrotron Light Source at Brookhaven National Laboratory, and the Cornell High Energy Synchrotron Source at Cornell University.

Collaborating with Earnest on the development of a second generation of automounting robots are Carl Cork of Berkeley Lab’s Physical Biosciences Division, and James O'Neill of the Engineering Division. The first generation system was developed in collaboration with Robert Nordmeyer, Earl Cornell, Derek Yegian and Joe Jaklevic of the Engineering Division, John Taylor of Physical Biosciences Division, Gyorgy Snell, who is now with Takeda Pharmaceuticals, and Ray Stevens of the Scripps Research Institute.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our Website at www.lbl.gov.

Additional Information

• For more information about Thomas Earnest, visit the Website at http://www.lbl.gov/pbd/about/people/earnest.htm
• For more information about Berkeley Lab’s Physical Biosciences Division, visit the Website at
  http://www.lbl.gov/pbd/default.htm
• For more information about Berkeley Lab’s Advanced Light Source, visit the Website at
  http://www-als.lbl.gov/