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NSF Funds $25 Million High Technology Center Led by UB

Seeing is believing. From telescopes to microscopes and beyond, progress in science has depended on inventions that allow us to visualize objects that we cannot see with our naked eyes. A revolutionary technology for seeing molecules and following their motions lies at the heart of a $25 million award from the US National Science Foundation (NSF) to the University at Buffalo, given on behalf of a nation-wide consortium of research organizations and institutes. The Hauptman-Woodward Medical Research Institute, which also serves as the Department of Structural Biology for UB, was very influential in securing this grant. The award provides for the creation of a Science and Technology Center (STC) designed to transform the field of structural biology, including drug development, using x-ray lasers. The Center goes by the acronym BioXFEL.

The award, which was announced at a press conference on November 6, is very prestigious. NSF selects just a handful of STC winners every four years from a pool of hundreds of applicants. The other winners in this year’s competition were Harvard and MIT. The establishment of this STC will put UB, HWI, and Western New York in the forefront of this technology. Although much of the money goes to institutions outside of Buffalo, It will also be good for the bottom line.

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What is an x-ray laser? Rainbows spread out all the colors of light before us. But past the edges of the rainbow are colors we cannot see. Beyond the red lies the infrared, which we sense as heat, and then “colors” that we use for telecommunication, such as radio waves. Beyond the violet edge are the ultra-violet, responsible for suntans, and then x-rays, familiar from our doctor’s office. X-rays are very penetrating and energetic, and can probe the atomic interstices of matter. The X-ray laser, which is sited at the SLAC National Laboratory at Stanford University, is an incredibly intense beam of X-rays, a relative of the laser pointers we see in lectures.

What are molecular pictures? The chemical formula for water is H2O, two atoms of hydrogen and one atom of oxygen. Picture an atom as a ball. A molecule of water has these three balls (atoms) arranged along a bent line, with the oxygen in the middle and the two hydrogens on the outside. Drugs are molecules with tens or hundreds of atoms, but we can make 3-D pictures of them too. Most drug molecules work by nestling up to (“targeting”) even larger molecules called proteins, and altering their functions. For example, penicillin kills bacteria by interfering with a protein whose normal job is to help the bugs create new cell walls after they divide. Penicillin was discovered by a lucky accident. Today, by making pictures of protein drug targets we can design drug molecules rather than relying on trial-and-error.

How do we make molecular pictures? In the method called X-ray crystallography we analyze patterns created when an X-ray beam strikes a crystal, and breaks up into a family of secondary beams that flash out in all directions. These patterns can be processed to provide pictures of the molecules that build up the crystal. Thus, crystals of water are what we call ice, and it is from X-raying ice crystals that we know the structure of the water molecule described above. As mentioned above, the new X-ray laser on which the Center is based allows us to use incredibly tiny crystals, which are much easier to make than the larger ones we need today. The technology will bring a whole new world of drug targets into our picture gallery.

So what is the science about? Structural biologists work to create amazingly detailed, three-dimensional pictures of molecules, through a process called x-ray crystallography. The method requires us to grow crystals of proteins, much as we made crystals of salt in 3rd grade. Such pictures provide a basis for rational design of drugs, and for an atomic understanding of life processes. For example, many of our current anti-AIDS drugs were developed using such pictures. But this method has limitations.

To overcome these, BioXFEL will be developing the technology and infrastructure to support an astonishing new x-ray laser beam developed at the Stanford Linac Coherent Light Source. The laser provides incredibly intense x-ray pulses that are incomprehensibly short¬–less than a millionth of a millionth of a second. These pulses act as flashbulbs that will allow BioXFEL scientists to freeze molecular motions and produce movies of them.

In addition this phenomenal beam helps us in other ways.

• It lets us use crystals a thousand times smaller than the ones we use now. Right now most attempts at crystallization fail. Because small crystals grow more readily, we will be able to study new and important drug targets.

• As the x-ray laser is upgraded, we may be able to study single molecules, eliminating the need for crystals.

Hauptman Woodward’s research contribution to BioXFEL will be an extension of its highly successful high-throughput crystallization laboratory. It will be developing a whole new set of technologies and protocols to understand grow, and manipulate the ultra tiny crystals that will be examined with the X-ray laser.

Outside of Buffalo there are six other participating research institutions: Arizona State University; University of Wisconsin, Milwaukee; Cornell University; Rice University, Stanford University; University of California, San Francisco.

Your correspondent will be director of the BioXFEL center. John C. H. Spence, PhD, Regents’ Professor of Physics at Arizona State University, will serve as the Center’s scientific director. The educational director is a UB professor, Dr. Margarita Dubocovich.

Eaton Lattman, PhD, is director of the Hauptman Woodward Research Institute. This column is part of an occasional series exploring news about science and technology in and around Buffalo.

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