A Cornell University-led research group comprising 25 faculty members from six institutions has been awarded a $19.6 million, five-year grant by the National Institutes of Health to build a structural biology research facility at Argonne National Laboratory's Advanced Photon Source (APS). The amount of the first year's grant is $4.6 million.

The scientists believe that the results of their research will have an important impact on human health care, pharmaceutical development and biotechnology. The goal is to apply the techniques of X-ray crystallography --- firing a beam of X-rays through a crystallized protein sample to determine its structure -- to the causes and treatments of human disease, including cancers and diseases of the immune system. Areas that will be investigated include cell-cycle regulation, DNA transcription, initiation and regulation, the structure and function of viruses and enzymes, and protein folding.

The research group is called the Northeastern Collaborative Access Team (NE-CAT) and consists of faculty from Cornell, Columbia University, Harvard University, Memorial Sloan- Kettering Cancer Center, Rockefeller University and Yale University.

The APS is a third-generation particle storage ring built by the Department of Energy at a cost of nearly $1 billion and is one of the most powerful X-ray sources in the world. The NE-CAT facility is just one of 34 being developed at APS through scientific collaborations and one of only a handful to focus on biological research.

The goal of the consortium is to determine the atomic structures of very large molecules, or macromolecules, such as proteins. However, Steven Ealick, professor of chemistry and chemical biology at Cornell and NE-CAT's principal investigator and organizer, noted that "the real focus is on protein complexes, such as the ribosome." This is the site within the living cell where proteins are synthesized from RNA. Ealick also noted the focus on research into transcription complexes, which cause DNA to be transcribed into another strand of DNA or RNA, and signaling complexes, in which one molecule communicates with another by sending out a signaling molecule.

"Up to this point, crystallographers mostly looked at individual protein components. Now the focus is turning to looking at how these components assemble to perform their function," Ealick said.

This research will be conducted taking advantage of what Ealick describes as "the extra brilliance" of APS's beam lines for studying these large complexes. Brilliance -- which is the intensity of X-rays emitted by atomic particles called positrons (they are the antiparticles of electrons) -- is achieved through the use of devices called undulators. APS is the only synchrotron in the United States that can regularly use these magnetic devices, which produce huge intensity peaks in the X-ray beam spectrum. Other U.S. synchrotrons, such as the Cornell High Energy Synchrotron Source, use older high-intensity devices called wigglers.

Ealick said that one of the most important applications of synchrotron radiation that will be pursued at Argonne is multiple wavelength anomalous diffraction, known as MAD phasing. This is a powerful technique used to more accurately image a protein molecule from a crystal. It does this by extracting so-called phase data from X-ray patterns measured at several different wavelengths and by looking at the differences in intensity of those measurements.

In addition to the NIH funding, the NE-CAT project also will receive $6.6 million from member institutions and $1.5 million from the APS. The sector will be developed in three phases, with the first X-rays expected about a year after the start of construction. "We are very optimistic that some really important structural biology will come from all this," said Ealick. In addition to structural biology, the team's biomedical research, he said, will involve cancer biology, immunology and virology, as well as the basic disciplines of biochemistry, cell biology, molecular biology and biophysics.

Each of the 25 researchers involved in NE-CAT heads a research group, which together include several hundred graduate students and postdoctoral research fellows who are training for careers in the biological sciences. Besides Ealick, Cornell researchers involved in the project are Jon C. Clardy, the Horace White Professor of Chemistry and Chemical Biology, and assistant professors of biochemistry Christopher Lima and Hao Wu, both at Weill Cornell Medical College.