Team gets grant to develop nano X-ray diffraction

The W.M. Keck Foundation has awarded a $900,000 grant to a team of scientists, led by David Eisenberg, for a research project, “Nano X-ray Diffraction of Biological Materials,” to develop tools that may someday reveal the secrets of cells in health and disease by providing precise pictures of the interacting molecules.

 

“Often the great breakthroughs in science come from new tools,” said Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a CNSI member. “Nano X-ray diffraction can reveal the three-dimensional atomic structure of intracellular organelles and aggregates that mediate the metabolism and pathology of cells. In contrast, nearly all present information on the atomic structure of cellular constituents has come from purified molecules, removed from cells.”

 

Eisenberg and his colleagues will exploit recent advances in the production of highly focused (nano) X-ray beams and free electron lasers, directing these beams onto biological cells and subcellular organelles, prepared by new methods for X-ray examination. They will then devise methods for collecting and interpreting the diffraction data.

 

This research offers the potential for very exciting applications. Among them will be to learn the atomic structure of the carboxysome, the organelle that removes carbon dioxide from the atmosphere, a process that is critical to sustaining life on Earth, and to learn which types of cells contain aggregates of protein in the amyloid state — akin to the deposits in Alzheimer’s and Parkinson’s diseases — but apparently part of normal function.

 

The same tools can exploit microcrystals and microdomains of larger crystals to yield far greater information, said Eisenberg, a Howard Hughes Medical Institute investigator, who holds the Paul D. Boyer Chair of Biochemistry and Molecular Biology.

 

"In the new work, we propose to study samples down to 1 micrometer (about 1/100th the width of a human hair) in cross section, including biological cells," he said.

 

The other principal investigators on the project are Todd Yeates, professor of chemistry and biochemistry and a CNSI member, and James Bowie, also a professor of chemistry and biochemistry and a member of Eisenberg’s institute.

 

Yeates has pioneered the structural biology of bacterial microcompartments and has used methods of X-ray diffraction to elucidate the structure of the shell-like enclosures of several of these microcompartments, purified and reconstituted as crystals. His goal now is to illuminate the structure of microcompartments, including their contents in cells.

 

Bowie is a leader on the structures of membrane proteins, which lie in the barrier between biological cells and the outside world. Membrane proteins are critical for capture and conversion of energy, and as receptors for drugs. Technical issues have slowed knowledge of membrane proteins. Bowie proposes using nanocrystallography to bypass these stumbling blocks. 

 

For more information about Eisenberg’s research, see his website. For more about Yeates’ research, go here. For more about Bowie’s research, see this.