"It must be really good machinery," she says.

The sperm’s tail is called a flagellum. A shorter version, called cilia, lines our respiratory tract and helps move mucous and foreign debris up and out to our noses and mouths. Cilia also are found in a wide variety of other places, not only in humans but also in most other animals. They line the gills of mussels and move water over the gills so that oxygen can be taken up and carbon dioxide released. They even seem to be involved in our early embryonic development at the time when the asymmetry in our bodies is established

Both flagella and cilia have the same internal structure, and this structure is the "machinery" that makes them move. In all species except for bacteria and the higher plants, from the single-celled protozoa to the human, and in all places that the machinery is found, the basic machinery is very similar.

The internal structure of a flagellum or cilium is a complex of 11 flexible tubules that are enclosed by an extension of the cell membrane. In cross section it resembles a bicycle wheel. Two of the tubules are in the center of the complex and form the hub. The other nine tubules, which are actually doublets, line the perimeter of the complex. The doublets have spoke-like protrusions that radiate inward and contain the motors that drive the movement, protein complexes called dyneins.

What makes a cilium or flagellum as a whole move is the movement of the outer tubules, and the direction or type of movement a flagellum makes is determined by which of the outer tubules move. If those on one side of the structure move, the flagellum moves in one direction. If those on the other side move, the flagellum moves the other way. But if all of them try to move at once, the flagellum cannot move.

It’s not known exactly what determines which of the outer tubules move, says Omoto. "It’s obviously a question of regulation." That regulation has been part of her work since she was a graduate student at the University of Wisconsin where she studied the protozoan paramecium. Paramecium are covered with cilia, and the direction of the ciliary beat determines whether the paramecium goes forward or backward.

"We still don’t know how that happens," says Omoto. But as she studied the means by which beat direction determines movement, she discovered that the central pair of tubules in the cilia rotates once in each beat cycle. Her discovery was controversial.

"Mostly nobody believed it," says Omoto, something she attributes to the fact that her data was in the form of electron micrographs, static images from which the rotation was inferred.

As a post doctoral associate at Princeton, Omoto solved the believability problem by using a small marine algae with exceptionally long center tubules that extend far beyond the outer ones. She glued the algae to slides by the end of the two tubules and used a 16 m.m. high speed movie camera to record the movement of the algae cell. The movie, which has since been made into a video, clearly showed that the algae cell body and thus the two central tubules rotate.

Since coming to WSU Omoto has used mutant algae with paralyzed flagella to determine how flagellar movement is regulated. Her working hypothesis is that the central two tubules specify which of the nine outer tubules move at any given time. She thinks that they do so by sending a message to the outer tubules that is delivered via the spokes. When the outer tubules receive the message, probably at a specific spot on the dyneins, they respond appropriately.

Flagella on mutant algae from the first group that Omoto analyzed were found to be missing either a part of the two inner tubules or a part of the spokes. Yet although their flagella are paralyzed under normal conditions, Omoto found that these algae can still move under some experimental conditions. This happens when there is low concentration of adenosine tri-phosphate or ATP, the energy currency of life at the cellular level, or when certain analogs of ATP are added to otherwise normal conditions.

Omoto believes that these results indicate that, for the paralyzed mutant algae, all nine outer tubules try to move at once at normal or physiological levels of ATP. In a normal algae, the central two tubules regulate outer tubule movement by specifying which of the nine can move. In mutants missing parts of the spokes or inner tubules, there is no regulation and the mutant algae’s flagella are paralyzed just as those of a normal cell are if all nine outer tubules move at once.

Omoto hopes that she will be able to determine what specific parts of dynein are involved in the regulation of movement by studying a second collection of mutant algae. The algae in this collection differ from those already analyzed in that the mutations are dominant rather than recessive. This difference allows her to learn a great deal more about the gene that has been mutated and the protein that is made from it.

Determining whether a mutant is recessive or dominant is not straightforward, for all of Omoto’s mutants are haploid, containing only one set of chromosomes. Omoto makes artificial diploid algae by combining a haploid mutant with a haploid normal alga. If the artificial diploid does not express the mutant phenotype and its flagella move normally, the mutation is recessive. The algae makes no mutant protein but only the normal protein.

When the artificial diploid expresses the mutant phenotype and its flagella are paralyzed, the mutation is dominant. The algae must make and assemble the protein from the mutated gene or the mutation would not be expressed.

Recessive mutants tell Omoto only whether or not a protein is necessary for the flagella to function. If the protein is made and assembled, the flagellum works. If the protein is missing, it does not.

Omoto uses her favorite analogy to explain. "It’s like a car," she says, "If you’re missing a tire or a spark plug, it won’t run." But that’s all you know, that you need these things. You can’t learn anything more about the tire or the spark plug if it’s just missing, she says.

But if the parts are there but changed, you can learn much more. If your tire has a huge bump on it so that the tire can’t rotate, the car won’t run. "This tells you much more about the tire and what’s necessary in its structure for the car to run," says Omoto. The more different types of defects you have in your tire that result in the car not running, the more you can learn about the structure and function of the tire.

The same is true for the dominant mutants. Because they make the mutated protein, you can compare this protein to the normal protein. You can determine what part of the protein has been changed and what specific parts of the protein are necessary for the flagellum to function properly.

"Once we know a lot about a protein, we can make deliberate changes or mutations in it’s gene in order to learn more about it," says Omoto. But with the dyneins, we know only little snippets of information, she says. We don’t know enough to make intelligent changes so that we can dissect its structure and function.