The Flow

By Eric Sauter

Jennifer Busby, the Scripps Florida associate director of proteomics, never could relate to organic chemistry—although she shone in other areas of science.

"I wasn't a mix-and-go chemist," she says modestly. Instead, she found herself drawn toward the analytical, eventually finding her scientific home in the field of mass spectrometry.

Busby is now an expert in mass spectrometry, a technique for calculating the mass or weight of molecules by measuring the ratio of mass-to-charge of a molecule that has been converted into an ion or electrically charged. Mass spectrometry can be used to identify unknown molecules as well as revealing their structural and chemical properties. Busby is particularly interested in using mass spectrometry to better understand the nature of proteins.

Born in Wheeling, West Virginia, Busby went to high school in Alabama. Her father was a chemist who worked in the steel industry, so as a child she made the rounds of the steel centers of America—from Wheeling to Oklahoma to Chicago. She was, she said, always a science kid and brought that interest with her wherever they went. She had genes on her side as well—in addition to her chemist father, her grandfather was a high school science teacher.

Busby did her undergraduate work at St. Mary's College, a small, all-women liberal arts school with the advantage of being across the street from Notre Dame, where students could go to get any special science equipment they needed.

"We had very small classes," she says, "and when you're studying chemistry, it's better to have six people in a small class. I think there were five chemistry majors and about 25 biology majors in the school."

Because of her non-interest in the mix-and-go side of chemistry, when she started to look for graduate schools, she chose to focus on mass spectrometry.

The Emergence of Mass Spec

The technology of mass spectrometry dates back to around the turn of the last century, when two British scientists, Joseph Thomson and Francis Aston, uncovered the principles of mass spectrometry and won the Nobel Prize for their efforts; in total, five Nobel Prizes have been given to mass spectrometry pioneers, the latest award in 2002.

In recent years, mass spectrometry has undergone something of a revolution, as dramatic advances in the technology, such as tandem mass spectrometry (basically a kind of Gatling gun mass spectrometer capable of handling multiple rounds of analysis) and improvements in bioinformatics, computers, and laser technology, now allow scientists to measure larger and more fragile molecules such as proteins.

For graduate school, Busby chose the University of Virginia and the laboratory of pioneering chemistry professor Donald Hunt, who is well known for his work in mass spectrometry, especially when it comes to analyzing proteins and peptides.

"His laboratory was the first to show the sequence peptides by mass spectrometry—the biological aspect of the technology," she says. "That meant we could work with peptides and proteins and that we could have biologic collaborations. It was a very practical model that was designed to move things forward; really, it was about how you get from point A to point B in an experiment."

After working in Hunt's laboratory, Busby moved onto MDS Proteomics, a contract research organization of nearly 250 people that did peptide mapping for various pharmaceutical companies, including Eli Lilly and Novartis.

It was there that Busby stepped deeply into what has now become her stock and trade—a proficiency that encompasses not only analytical chemistry, but also collaboration.

Collaboration was certainly part of the attraction of coming to work at Scripps Florida, that and the challenge of starting up the proteomics core facility. There, Busby now has the opportunity to create data spreads for Scripps Florida scientists and for big outside clients like the University of Miami Medical School, which has no mass spectrometry capabilities of its own.

"At any given time, we have between six and 10 ongoing collaborations of various sizes," she says. "Overall, we have worked with around 90 percent of the Scripps Florida faculty, but there are always one or two outside collaborations. I'm always asking when the samples are getting dropped off. Keeping up that flow prevents things from backing up and everything getting overwhelmed."

Proteomics Ahead

In these collaborations, Busby works in the science of proteomics, which is essentially drilling down, focusing on smaller and smaller biological regions to understand the basic mysteries of proteins.

"We know a lot about how proteins function, but most of the things that occur are not well understood," she says.

She believes this rigorous focus on mechanisms reveals more useful answers than a large-scale approach. "Looking at signaling events that can be changed by phosphorylation that occurs with drug treatment can give you more useful answers than looking at whole protein changes," she says. "If you go to the nucleus, your answer will be much better still."

One of her collaborations involves work with Associate Professor Paul Kenny's laboratory, which has Busby looking at neuron models of addiction, homing in on subsections and markers.

A recent collaborative study with the Bascom Palmer Eye Institute at the University of Miami involved the proteomic analyses of the optic genes of the Zebra finch, a songbird popular with researchers because their songs affect the quality of their lives.

"It has been shown in finches that how well they learn their song is important to how well they live," Busby says, "and that there is a neurological connection between vocalizing and living. They also have optical issues that appear to be similar to the demyelization of multiple sclerosis—their optical proteins are similar to early stage of the disease."

Busby has had as much opportunity to collaborate in her own life as she has in her scientific one. She and her husband Scott (he works in Scripps Florida's Nuclear Hormone Receptors program) were recruited in 2004 by Pat Griffin, the head of translational research, and they had to learn to balance their work, marriage, and a new baby, almost all at once. That collaborative effort has worked out just fine.

"Our marriage in science is working well," she says. "We had the first Scripps Florida baby—who's now the same age as Scripps Florida. It's easy for either one of us to walk down the hall and say, 'Hey, I'm running late, can you pick up Christopher?'"

Busby isn't afraid of shifting roles, and seems to know how to make it work no matter what the forum.

"In terms of mass spectrometry," Busby says, "there's a lot of room for women in developing methods. Once you get into building the machines, it's pretty much all men."

Not on her watch, however. Everybody works on the machines to make sure that they continue to work properly and that the various projects keep moving forward.

"Oh, sure, we take them apart all the time," she says. "Basically they need to be cleaned. In fact, one of mine is going down right now because we're changing electron multipliers. It's easier for us to set aside time to do these kinds of routine maintenance than wait around for someone else."

Send comments to: mikaono[at]scripps.edu

As associate director of proteomics at Scripps Florida, Jennifer Busby draws on her skills in analytical chemistry and in collaboration.