Courtney Miller's Compass

By Eric Sauter

Courtney Miller, the new assistant professor in the Metabolism and Aging and Neuroscience Departments at Scripps Florida, was born in Oregon but grew up in the San Francisco Bay Area. That's where her sense of both the world and her own role in it were formed.

So was her sense of the dangers in it. After her parents enrolled her in a private school—"because the public high school was just too risky"—she would drive herself to school in Silicon Valley rush hour traffic and then to diving practice, all the while aware that just beyond the boundaries of her own neighborhood in east San Jose, things were quite different.

"There were a lot of gangs," she said. "I was safe, but I knew first-hand the realities of the world—some of the kids I grew up with didn't make it because of gang violence. When asked if this has made her a fatalist, Miller is quick to respond, "Actually, I'd say all that reality so early in life has made me an optimistic pragmatist. And clear that I needed a plan."

It is that view that took her from the University of California, Santa Barbara, where she graduated in Biopsychology, to the University of California, Irvine, where she earned her Ph.D. in Neurobiology, to University of Alabama at Birmingham, where she did her postdoctoral work in learning and memory. By the time she finally arrived at Scripps Florida, she was still utterly fascinated by what goes on in people's heads.

"I've always been interested in the mind and how it works," she said. "In my junior year of high school, when colleges sent out their recruiting material, I got one that listed biopsychology and I asked my chemistry teacher about it. He explained neuroscience and I said, 'That's what I want to do, got it, check that off.' I went to Santa Barbara because it was one of the only universities offering a neuroscience major to undergraduates and the department chair was a neuroscientist."

Miller was also a gymnast but soon left the gym for the high board: "I decided I wasn't going to be an Olympic-caliber gymnast, but I was good at throwing myself around, doing flips, and, bonus, with diving it's a softer landing—as long as you do it right!"

Her diving helped pay for school, just not as much as her gift for science did—she received one athletic scholarship and two academic ones. But like Jack Sparrow's magical compass that shows you the direction of the thing you want most in the world, it was her rock solid sense of purpose that was probably the most valuable of all.

"It's true, I had—and still have—a surprisingly well defined plan for myself," she said. "It's been that way for a long, long time."

Memory and Learning

In the course of her academic career, Miller has managed to add a significant amount of new knowledge on the role memory and learning play in our lives.

Her graduate training was in drug addiction, specifically the component of memory that drives relapse. In a 2005 study, published by the journal Neuron, she and her advisor John Marshall at UC Irvine showed that when given a choice between two separate rat-sized rooms, the rodents preferred the one where they remembered getting cocaine on previous days.

The scientists' research showed that a master neural regulatory pathway, triggered by a molecular switch called ERK, was turned on during the room-selection process. Moreover, they found that if they blocked the ERK pathway, the animals basically forgot about their interest in cocaine.

It was the first study to identify a molecular mechanism that blocked both retrieval and reconsolidation of any type of memory.

"We did that study in 2005," she said, "and I thought, 'There's a lot more to figure out about this.' But I also knew I needed more training at the molecular level."

That brought her to Alabama and another breakthrough study.

Her postdoctoral work in the laboratory of David Sweatt, the chair of the Neurobiology department at the University of Alabama at Birmingham, focused on the emerging science of epigenetics, the study of changes in gene function without a change in DNA, something that has only recently come to the fore of neuroscience.

If the traits can't be inherited, what's the point? Quite a bit as it turns out.

"We've found that the brain uses these epigenetic mechanisms for its own purposes and in its own fashion. This is something that wasn't on the radar of neuroscientists until about five or six years ago. It's turning out to be something of a surprise for epigeneticists, too, that it seems to work differently in the brain, that we can have these changes and that they can be both dynamic and lasting."

Published in 2007, also in the journal Neuron, Miller and Sweatt's study was the first to show that a process called methylation played an integral role in regulating gene activity involved in memory formation.

Although still not entirely understood, it is widely accepted that DNA methylation plays a role in controlling whether or not a gene is turned on. In the process, a specific section of DNA has a methyl molecule added to it. Once attached, the methylation process cuts the gene off from any possible transcription, repressing its function. Traditionally, methylation has been studied only in terms of development—the process helps during embryonic cell differentiation, allowing cells to become skin cells, hair cells, nerve cells, etc., during early development--or disease states, such as cancer.

Miller and Sweatt thought there might be more to the story up in the brain.

"We believed that there could be environmental influences in an adult mammal's life that could have an epigenetic impact," Miller said. "It goes back to the question, 'How do you physically maintain a memory?' The proteins that encode these memories are constantly being turned over, so we thought the brain might use DNA methylation as a method of preservation—because of the ability to permanently mark DNA."

A Marriage in Science

It was also at the University of Alabama at Birmingham that Miller met her husband, neuroscientist Gavin Rumbaugh, also an assistant professor at Scripps Florida.

After falling in love, they discovered that their complimentary scientific backgrounds could make them better at their jobs. Both interested in how the minds works, Rumbaugh moves up from the level of molecules and the synapse, while Miller works back from the opposite end—circuitry and behavior. The couple is writing several papers together.

Given this shared-interest-but-different-approach, you'd think they'd spend all their time talking science, but you'd be wrong. "We spent plenty of time in mad scientist mode, putting our brains together and coming up with things neither of us would have on our own. But we also love life and love living in Jupiter. You'd be just as likely to find us at the beach or in the kitchen cooking a gourmet meal."

"Memory, aging, mental illness, and addiction are tied together," she said. "They all use the same systems; they just show different changes. That's why it's so complicated, because you have all of these signaling pathways and interactions and circuits that can go wrong. We're not even close to understanding how the brain or memory works. I don't think any of us will ever be out of job in our lifetime, but we're making progress in the meantime."

Send comments to: mikaono[at]scripps.edu

"I've always been interested in the mind and how it works," says Assistant Professor Courtney Miller. (Photo by James McEntee.)