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Your research focuses on cell cycle control in yeast. What makes yeast a good model system for studying the cell cycle? Is it just that they're easy to grow?
They're easy to grow and they're easy to manipulate genetically, and we have an accumulated body of tricks and knowledge from years of working on it. Also, it turns out that the machineries to do central cell cycle processes like cell polarity or cell cycle are high conserved, so that we hope what we learn will be applicable to many cells.
Your work has uncovered a checkpoint control in the yeast cell cycle - when the yeast is preparing to bud, and something adverse happens (temperature drop, moisture stress, etc.) the yeast knows to put its plans for mitosis on hold. Is that about right?
Yes, somehow it knows whether or not it has built a bud. These environmental changes, like temperature rises in particular, can transiently inhibit bud formation by disrupting the actin cytoskeleton, and remarkably, yeast seem to know what shape they are - whether or not they have a bud. We're trying to figure out how they know what they know.
And you think that maybe it knows that it has a bud because of the interaction with the actin structure inside?
We think, actually that the sensing of cell shape is due to another family of much less famous filamentous proteins called septins. In yeast, septins form a structure that's at the neck between the mother and the bud and that seems to be how they know whether or not they have a bud - whether the septins are in a geometrically flat or tubular environment.
You're in the Pharmacology and Cancer Biology department at Duke. What's the tie-in between your work and pharmacology and cancer biology?
The tie-in with cancer is that, among the most important things that get derailed as cancers develop include the controls on the cell cycle and on cell migration and behavior. Cancer cells ignore what should be the normal regulatory mechanisms that keep those in check and they over proliferate and migrate where they shouldn't. Understanding the basic mechanisms by which cells control their cell cycle and control their polarity will give us some insight into how those things are misregulated in cancer.
I noticed on your CV that you earned your undergraduate degree at Cambridge in England, but you don't have a characteristic British accent, and it's definitely not from North Carolina, either. Where does your accent originate from?
I think it's compiled from all the places I've been. I was born in Argentina, and I did my high school and college in England and then moved to the U.S., and I've been here ever since.
What's next for your lab?
We're really interested in understanding the establishment of cell polarity. One of the insights we've had in the last many years from multiple labs is that, although cells normally polarize n a direction that makes sense, these directional sensing mechanism are overlaid on what is probably a more ancient and highly conserved mechanism to polarize cells, which is to determine a single axis - a front and a back. That mechanism can work even if there is no spatial information about where a cell should polarize. All the molecules somehow agree on a single site, which can be totally random, to be the front. We're trying to figure out how they do that.
What do you think is the most understudied microbial system?
I fell in love, some time ago, with the bean leaf rust fungus, which is one of many who do this remark behavior called thigmatropism. The spores of this fungus land on the leaf of a bean plant and germinate and send out a germ tube, which then hunts around until it finds the stomatal pore opening on the surf of the leaf, at which point it can penetrate inside there and become the intracellular parasite of the plant that it wants to be in order to complete its life cycle. I think it would be fascinating to find out how they do that.
What is your favorite microbe? Why?
I'd have to go with the budding yeast because the accumulated knowledge of the field and tricks have been developed allow us to probe with unprecedented accuracy what's actually going on inside the cell.
What is something about you that most people don't know?
Anything. I don't think I'm well known, so most people don't know anything about me.