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Next-Generation Crystallography

 

E_LattmanHWI is part of a consortium of eight research universities and institutes that has been awarded a $25 million Science and Technology Center (STC) grant from the National Science Foundation to advance the use of a recently developed free-electron x-ray laser (XFEL) in the imaging of biomolecules such as proteins. UB was awarded the grant on behalf of this distinguished group, and HWI's Principal Research Scientist Eaton Lattman, who also serves as Professor of Structural Biology at UB, is the Center Director. Our Center is called BioXFEL.

What does this grant mean to HWI, scientifically and operationally? The award is very prestigious. NSF selects just a handful of STC winners every four years from a pool of hundreds of applicants. The establishment of this Science and Technology Center at UB and HWI will put Western New York in the forefront of development of an exciting new technology. It will also be good for our bottom line.  Although most of the money goes to the six institutions outside of Buffalo, the funds remaining with HWI still make a significant impact.

So what is the science about, and how will we contribute? HWI scientists work to create amazingly detailed, three-dimensional pictures of molecules, through a process called x-ray crystallography. Such pictures provide a basis for the rational design of drugs, and for an atomic understanding of life processes. For example, all of our current anti-HIV drugs were developed using such pictures. But this method has many limitations.

Dr. Lattman talks about the
BioXFEL grant:

• NSF Grant to Reveal New
  Universe of Drug Targets
• Crystallography and Lasers
Research Groups
• Educational Aspects

Molecular pictures are derived from the patterns created when an x-ray beam bounces off a crystal, and breaks up into a family of secondary beams that flash out in all directions. 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.

What else can this phenomenal beam do?

The laser will let 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 that crystallize in smaller quantities. As the x-ray laser is upgraded, we may even be able to study single molecules, eliminating the need for crystals.

HWI’s research contribution to BioXFEL will be an outgrowth of our highly successful high throughput crystallization laboratory.  We 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.

bioxfel_logo BioXFEL expects to provide the scientific community with a complex and valuable toolkit that will advance XFEL science on a broad front including: 

• Hardware and software innovations and developments  that will enable facile conduct of an array of XFEL structural biology experiments spanning a broad range of specimen types and dynamic regimes.

• A portfolio of successful structural projects providing important insights in their own right, and illustrating the capacities of the XFEL to the scientific community.

• A varied community of talented scholars, both in the US and world wide, with deep interest in and commitment to XFEL science, who will nucleate and promote new projects and development.

• Broadened public awareness of XFEL science in particular, and of biological imaging in general.

The grant was awarded to the University at Buffalo, SUNY. The other participating research institutions are: Cornell University; Hauptman Woodward Medical Research Institute; University of Wisconsin, Milwaukee; Arizona State University; Rice University; Stanford University; University of California, San Francisco CFEL Science, Lawrence Berkeley National Laboratory, Lawrence Livermore National Laboratory, University of California, Davis.

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