The article contains a unique technique—FIONA, or Fluorescence Imaging with One Nanometer Accuracy—which is very useful, combined with the solution to a well-known problem in molecular motors—namely, that myosin V (a particular type) moves in hand-over-hand fashion.

Both. The first part of the paper describes FIONA. The second part of paper uses FIONA to answer how myosin V moves. The technique of FIONA is certainly worthwhile in that we and others have already gotten other papers using the technique. For example, we have a paper on how kinesin moves (Yildiz et al., Science, 2004), how myosin VI moves (Yildiz et al., J. Biol. Chem., 2004), and most recently how the motors kinesin and dynein move cargo inside a cell (Kural et al., Science, 2005). Others have picked up the technique as well, publishing papers in PNAS and Nature Structural & Molecular Biology.

I started out in the world of fluorescence, knowing little or nothing about molecular motors. During my postdoc years, Roger Cooke, from UCSF, suggested we do an experiment on muscle myosin, using a new fluorescent technique that I discovered. I was game. From there, I eventually learned about "unconventional" myosin and kinesin etc., and continued with new techniques in fluorescence.

FIONA is just a better way to find out where a dye is located. The standard diffraction limit of light says that you can locate an object, no matter how small, to only approximately the wavelength of light divided by two, or about 250 nm for green light. In essence, the picture of a fluorescent object (think of a tiny light bulb) looks like a mountain, with a width equal to 250 nm. But if you collect enough light (i.e., enough photons), the mountain has this width, but it rises to form a nice sharp peak. It’s much like looking at a mountain on a clear day—the peak may be very wide (say a 1/2 mile wide), but the position of the peak can be located very accurately (say within a few meters). It turns out with FIONA we collect a lot of photons and can locate the center to about 1 nanometer, or several hundred times better than what people are used to doing.

We then applied the technique to understand how myosin V moves. Myosin V is a molecular motor involved in moving cargo around a cell. It’s a dimer, meaning it has two legs. It’s long been wondered if myosin V "walks," that is, moves each leg "hand-over-hand," or moves like an inchworm. Because we had such good spatial resolution, we could tell that myosin V (and all other motors tested) walk hand-over-hand.