College of Liberal Arts and Sciences at Iowa State University

Spindle matrix

Basic science: Bringing back the matrix debate.
Does it exist or not?

That's what cell biologists have been asking since the 1960s about a molecular matrix, or supporting "under layer," that is believed to help the process of basic cell division.

Two Iowa State researchers are making headway in convincing others that the "spindle matrix" exists. Kristen and Jorgen Johansen, both professors of biochemistry, biophysics and molecular biology, have identified four "matrix protein candidates" and are using mutant fruit flies to confirm the proteins' function in cell division.

It's basic science with far-reaching applications into human health.

"Cell division is at the fundamental crossroads of life," Kristen said. Jorgen added that most types of cancer and some birth defects occur because "something had gone wrong with cell division."

For decades scientists have known about the spindle, so called because of its shape. A spindle is an arrangement of protein filaments that are needed to segregate a dividing cell's two sets of chromosomes.

Some 40 years ago it was proposed the spindle needed a matrix in order to move the chromosomes. However, not all cell biologists concurred.

The Johansens' matrix research, which has received National Science Foundation funding, was highlighted in a Nov. 30, 2007 article in the journal Science.

"We have the proteins identified by virtue of where they go and the dynamics of their distribution," Kristen said. "The real key will be to get down to the function of these molecules."

"We have enough molecules - more than we can handle," Jorgen said. "So the idea now is to show that this matrix does what it's supposed to do, which is to stabilize the spindle and be involved in generating the forces behind chromosome movement."

Jorgen added that scientists are curious to know how the chromosomes are pushed apart. "How the proteins actually exert the force, nobody really knows. If such a matrix exists, it would speak to that."

Kristen "stumbled" into the matrix research while in graduate school. "I was raising antibodies against a protein I was studying then," she said. "One of the antibodies didn't recognize the protein, but it cross-reacted with something in the nucleus."

Her grad school research commitments prevented her from pursuing the mystery at the time, but she was curious enough to keep the antibody. When she and her husband arrived at Iowa State, they conducted some more experiments. Using higher-resolution instrumentation, they saw a "spindle-like structure" forming in the nucleus. It surprised them.

"It was all strange," said Jorgen, "because there was nothing in the literature about things that reorganized in the nucleus to form a spindle."

The work led to the identification of the four proteins. Through additional lab work, the Johansens believe that a substance, the matrix, exists as a platform of sorts on which the spindle can develop.

Little work on the matrix question has taken place in recent years because scientists have not, as Jorgen said, "had a good grasp of the molecules." Now the work can progress, including understanding its role in humans.

"So now we have the molecules [proteins], there is no doubt about it," Jorgen explained. "But it's still open if those molecules also exist in humans. This is what we all want to know."

"It's a good illustration of the value of basic research," Kristen noted. "You can find interesting things and follow them and make some significant advances."