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The pro team for proteins: Instrumentation facility allows researchers to tackle 'hardpart' of geonomics quest

By Amy Agronis on June 30, 2000 in University

With the race to map the human genetic code just completed, the new frontier in genetics looks a lot like a lab in the basement of Hutchison Hall.

There, scientists work not on deciphering the genome but what they say is the far more daunting, yet promising, task of understanding how it works.

Research at the newly revamped Molecular Structure Facility centers on the proteins out of which all living things are built and which are assembled according to the DNA blueprint.

"I think the bottom line of biology is protein because proteins are doing all the hard work for the cellular functioning. The DNA is just information," says Young Moo Lee, a protein chemist who directs the lab full time for the Office of the Vice Chancellor for Research.

Over the past two years, Lee has worked to merge two existing campus labs to combine the best of classic biochemical tools and state-of-the-art instruments for identifying and characterizing proteins. The 4,500-square-foot lab has expanded its research staff and added sophisticated equipment using federal grants and UC Davis funds.

For UC Davis, the strengthened lab represents not so much a new emphasis but a continuing focus on protein biology. "In the last several years, many people abandoned protein chemistry. We didn’t," Lee says.

"From the mid-1980s to mid-1990s, a lot of people were more interested in molecular biology at the DNA level, not at the protein level. Now they are coming back to the protein level. … It’s a paradigm shift."

Mapping the human genome was a monumental task, involving identifying and putting in the correct order more than 3 billion chemical base pairs. Two rival teams of scientists announced in Washington, D.C., on Monday that they had completed a rough draft of that map.

Yet Molecular Structure Facility staff researcher Roger Mercer says that in comparison with what’s to come, that was "the easy part."

"Now comes trying to understand what all that means."

By studying proteins in healthy and diseased organisms, scientists hope to gain a better understanding how diseases work and ultimately develop better diagnoses, prevention and treatment.

First to merge with mass spectrometers

Lee says at least 200 labs across the United States identify and sequence proteins. But he believes UC Davis is the first university to merge classic protein biochemistry tools with state-of-the-art mass spectrometry instruments.

Mass spectrometers have long been used by organic chemists to determine structural and chemical information about molecules. However, only in recent years have the instruments been successfully adapted for analyzing large molecules like proteins.

Lee says directing a lab equipped with both conventional analysis tools and mass spectrometers has been his dream since he came here in late 1994 after working at a Bay Area biotechnology firm and Stanford University.

About a year ago, the Protein Structure Lab moved from Surge I to combine with the Facility for Advanced Instrumentation in Hutchison Hall.

Lee says the lab was combined for functional reasons: to better assist UC Davis researchers and to support the campus’s Genomics Initiative. The merged lab is more efficient for scientists, who might otherwise have to send their samples to two facilities, he says.

Robert Rice, a UC Davis environmental toxicologist, says having the lab on campus has helped him in seeking grant funding for his research on how toxic chemicals affect cell function.

The lab’s mass spectrometers are so sensitive that they can analyze samples that contain too little material for classic protein sequencing tools to measure.

A really huge asset

"It’s very hard to have access to that kind of instrumentation," he says. "It’s really a huge asset. I think we are a little bit ahead of most other places."

While half the facilities’ users are from UC Davis, the other half are located around the globe. Scientists from as far away as Japan, Taiwan, Korea, Australia, Italy, Mexico, Canada and Denmark prepare their protein samples in gel and ship them overnight to UC Davis.

University of Kentucky chemist Tae Ji ranked the lab among the top 10 percent in the nation for its ability to analyze proteins with the highest sensitivity and accuracy.

"Dr. Lee did an excellent job analyzing our protein samples and the results were unambiguous and convincing," Ji says in an interview conducted via e-mail.

Ji, who has spent three decades studying a human pregnancy hormone, says the analysis was done so quickly that his team was able to publish the results and include them in an application to renew its grant with the National Institutes of Health.

"Dr. Lee’s intellectual and technical contributions were so impressive, substantial and deserving that he shared co-authorship of one of our publications," he says.

Ji says he knows of colleagues who have found similar success at the UC Davis lab.

University of Wyoming reproductive biologist Thomas Hansen turned to UC Davis on Ji’s recommendation after years of unsuccessful analyses at other labs.

Helped clone cow uterine DNA

The UC Davis lab was able to perform a partial amino-acid sequence that enabled Hansen to isolate and clone some cow uterine DNA, Ji says.

Lab researcher Mercer says UC Davis has been able to develop a sophisticated lab by pooling campus resources, rather than leaving it to individual departments to buy the expensive machinery like many other campuses do.

The lab serves scientists across campus -- from biologists and biochemists to engineers and geophysicists.

The lab’s newest equipment -- including a half-million-dollar hybrid mass spectrometer installed last December -- was purchased with money from the National Institutes for Health, the UC Davis New Initiative Reserve and the Office of the Vice Chancellor for Research’s equipment-matching funds.

The facility now has four protein sequencers, several advanced mass spectrometers, two state-of-the-art amino acid analyzers, a two-dimensional gel electrophoresis system, several high-performance liquid chromatography systems, two capillary high-performance liquid chromatography systems and a DNA synthesizer.

Staff is the key to success

More important than the instruments, Lee says, is the expertise of the researchers who use them.

Some protein work, like amino-acid analysis, is difficult to do well, says Lee.

Lee says Jack Presley, a staff research associate who specializes in amino-acid composition and protein-structure analysis, is so well known in the field that he draws clients to the lab.

This year, the lab also hired Fan Xiang, who previously worked at the Pacific Northwest National Laboratory under one of the world’s leading scientists in biological mass spectrometry, to work with Mercer.

Lee’s careful attention to the minute details of sample preparation has been credited with the successful analysis of even the most hard-to-work-with samples.

The protein structure lab’s reputation is so well known that when the equipment manufacturer Beckman sold a dozen amino-acid analyzers to the Chinese government, Beckman asked researchers at the Davis facility to train the new owners.

When Hewlett-Packard developed a new protein sequencer, the Davis lab was selected as one of a handful of five beta test sites across the country.

"The expertise and the equipment of the Molecular Structure Facility will put the campus in a wonderful position to make an exciting contribution to genomics and proteomics," says Vice Chancellor for Research Kevin Smith. "I can’t wait to see what the future holds for us."

Vivian Carmichael of the Office of Research contributed to this report.

Media contact(s)

Amy Agronis, Dateline, (530) 752-1932, abagronis@ucdavis.edu

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