SA: You also know that G¿nther Blobel received the Nobel Prize a few years later, and, in fact, 23 of the Lasker Award winners won the Nobel Prize between 1980 and 1996. How do you feel about that?
RM: Well, you know [laughs], I would be very pleased, but I don't think about it. I am just concentrating on my science. I am already very pleased with how much people have seemed to have appreciated the work we have done here in the lab.
SA: What are you studying at the moment?
RM: Several things, and they are all an extension of the work we have done. One of the things we are trying to understand in more detail is: How do the ions go through the pore at the high rate that they do? The structure has allowed us to make initial hypotheses, but a higher resolution structure, combined with functional measurements, will allow us to test some of these hypotheses and understand the mechanism in more detail. That's one problem that we work on. Another problem is, there are different kinds of potassium channels. The pore of all potassium channels that we know of is very similar, and what this structure has taught us is a great deal about how the ions go through. But channels also open and close--that process is called gating--and we still don't know very much about gating.
There is one particular and important kind of gating that is called voltage-dependent gating. Certain potassium channels open and close depending on what the membrane voltage is. That's an interesting thing because it is in fact the ion channels themselves that set the membrane voltage. So a potassium channel opens, and it sets the membrane voltage, and yet the membrane voltage also sets whether it's open. That kind of property is called recursiveness, so you would say the molecule is recursive: its action controls something, and that same something controls the channel, feeds back on it. We don't really understand how a channel can sense the voltage and open and close in response to it.
We know some things. From the work of many laboratories, we know the parts of the channel. So the voltage-dependent channels have an additional group of amino acids that is not present on the bacterial structure we solved. The pore, the channel part, the hole down the middle of a voltage-dependent potassium channel would be very similar to the channel we solved. It has an additional part that allows it to sense the voltage. We don't know what the structure of that is, and we don't know how that marvelous switch works. So that's one thing we focus a lot on in the lab, to solve the structure of a voltage-dependent potassium channel.
SA: How about the long-term future? Do you think you will always work on ion channels?
RM: I would say, I never know. I really enjoy working on them. I love working on them--but also sometimes, as a scientist, I find change good for me. I have been studying channels now for a long time. I began my postdoc probably in 1986 or 1987, that's when I entered science. I worked with Chris Miller at Brandeis for three years, and then in 1989, 11 years ago, I went on my own, and I've been studying channels for the first half of that using electrical kinds of measurements, studying the function of channels, and then for the second half of that, I adopted structural biology techniques, using crystallography to see what they look like. So that change, adopting new techniques, kept me fresh and happy and thinking about new things.