Originally created 03/11/01

Field of protein analysis takes center stage



PITTSBURGH - The revelation last month that humans have surprisingly few genes - perhaps 30,000, only twice as many as a worm - may have been a blow to the ego of Homo sapiens, but it is proving a boon to the emerging field of protein analysis.

If the number of genes doesn't fully reflect the complexity of humans, the thinking goes, then it may become even more critical to understand the whole array of human proteins, the stuff produced by those genes. Knowing which proteins are produced at what time in which body cells could provide important insights into the diagnosis and treatment of cancers and other diseases.

But before this new field of protein studies, called proteomics, can really take off, technologists need to develop new, efficient ways to identify and analyze proteins in large quantities.

A number of researchers and companies are at work on this problem.

A decade ago, it might have taken weeks to simply identify a protein, said David Lubman, a University of Michigan chemist, and perhaps half a year to figure out the sequence and types of amino acids that comprise it. But if proteomics is to fulfill its promise, doctors and researchers will need to routinely measure thousands of proteins in a single cell in a matter of minutes or hours.

New techniques that use mass spectrometry - a method for precisely determining the mass, or weight, of tiny particles - already is speeding protein identification, as will new "lab-on-a-bead" technologies that might allow proteins to be optically identified, much as a grocery scanner reads a bar code.

"We can only guess how many (types of protein) are made," said Lubman. "We haven't seen them all."

But proteins, which make up the structure of organs and tissues and serve as enzymes and hormones for regulating body processes, far outnumber genes.

Not only can one gene often produce two or more proteins, but proteins can interact with each other to form more complex molecules, Lubman said. Some scientists have reckoned that the number of gene products ultimately might number in the millions.

All of those proteins aren't produced all of the time and not in every cell. In his lab, Lubman is comparing the protein profiles of cells in culture as they progress from normal through precancerous stages to malignancy.

This type of analysis eventually will help in diagnosing cancers, in tailoring chemotherapy for each patient and in monitoring treatment effectiveness, said Lubman.

Some researchers hope that certain proteins or combinations of proteins may serve as biomarkers, which could serve as an early indication of cancer if detected in a blood test.

Similar hopes have been expressed for genomics - that the pattern of genes turned on and off in each cell might reveal the health status of a cell. Either or both approaches may yet prove effective, though proteomic researchers argue that protein profiles might be easier to interpret.

"What you get with genomics is like a Picasso painting of a woman" - enough features to create the impression of a woman, but nothing easily recognizable, said Donna Felschow, a field research scientist with Ciphergen Biosystems of Fremont, Calif. "With proteins, you get a Da Vinci - you see the Mona Lisa."

Ciphergen makes a protein analysis tool called the ProteinChip. It uses a specially treated strip to isolate those proteins that interest a researcher, then uses a laser to dislodge and send them into a mass spectrometer.

Shuming Nie, an analytical chemist at Indiana University, said another technology that can help with this sorting and analysis is the so-called lab-on-a-bead. These tiny, microscopic particles are each specially treated to bond with a certain type of protein or gene. Researchers can then rapidly determine which proteins or genes are present in the sample by using lasers or other devices to see which beads have proteins attached.