Similar to photography, Barron’s domains of science and engineering require a good deal of painstaking trial and error — skillfully identifying what works and what doesn’t and understanding why.

Barron is creating new synthetic polymers — large molecules strung out like strands of spaghetti — for applications in biotechnology and medicine, including DNA sequencing. She knows where she wants to end up and what problems she wants to solve, but the trick is to design molecules with the appropriate physical and chemical properties to get her there.

Along the way, while posting many successes, she and her students have had ideas that didn’t always pan out. But for Barron, dead ends lead to new knowledge and new possibilities. She is constantly learning and moving forward. And now Barron is poised to deliver some gems.

Forging New Frontiers
“Her research is not traditional for a chemical engineer,” says E. Terry Papoutsakis, Walter P. Murphy Professor of Chemical Engineering, of his colleague. “Annelise blends chemistry and biophysics, a unique mix of disciplines. Because she understands the two so well and can integrate them, she is able to bring about important new applications while answering fundamental questions of science.”

Chemical engineering involves applying chemistry to solve technical problems. The field typically has focused on scaling up chemical processes for mass production and distribution. Oil, synthetic rubber, automotive plastics, pharmaceuticals and even Tupperware® are examples of products that rely on chemical engineers. Now the field is also moving the other way, down to the molecular level, allowing Barron to carve out her own niche.

“I’m interested in something different,” says Barron, who packs a disproportionate amount of energy into her 5-foot-2-inch frame. “I want to know how a polymer’s chemical structure controls its physical properties. With that knowledge I can create new materials with superior properties. I love the chemistry, but what I love most is taking things all the way through to the point of application.”

As she designs and synthesizes novel polymers, Barron has two major goals. One objective is to dramatically speed up DNA sequencing and genotyping by designing materials that enable the necessary processes to be miniaturized, leading to widespread applications. The other is to mimic biological molecules called polypeptides, including a human lung surfactant protein and anti-microbial peptides, to improve human health (see sidebar).

To attack these problems, Barron has assembled a large research group — currently 13 graduate students and two postdoctoral fellows. They are spread out over five laboratories in the Technological Institute, including two new organic synthesis labs into which she moved recently upon receiving a joint appointment with the Department of Chemistry. (Barron is also a member of the Department of Biomedical Engineering.)

A tour of her group’s research space reveals a large lab that, along with sophisticated research instruments, houses four tropical fish tanks. One of them contains the colorful and aggressive state fish of Hawaii. “The humu-humu-nuku-nuku apua’a,” says Barron, rattling off the mellifluous mouthful easily. “Something with that unusual a name is worth memorizing.”

Barron notes that the long name of this small triggerfish, which is a department mascot of sorts, somewhat resembles a polymer in its simplest form. A polymer is a large molecule made up of many simple repeated units linked together in a long chain. (Think of the “humu” and “nuku” as different chemicals, such as carbon or nitrogen.) The chain has a particular architecture, based on sequence and overall length, from which the polymer derives its properties. DNA, RNA, proteins and plastics are all polymers.

Barron, who already has two patents to her name, is bent on making her mark by designing useful new polymers, molecule by molecule.

“Annelise is one of the most important people in chemical engineering,” notes Papoutsakis, who has known her since her arrival at Northwestern in 1997. “While pushing forward new fields of study, she’s ambitious and hardworking and also equally wonderful and personable.”

Finding Her Way
Barron didn’t always want to be a molecular engineer.

Her journey began in Milwaukee in 1968, the year she was born to a Wisconsin woman of Swedish and English heritage and a Bolivian immigrant who had come to the United States at the age of 21 with $300 in his pocket. Her parents divorced when Barron was 2, and her mother soon remarried. When Barron was 5, her family moved to Fairbanks, Alaska, where her stepfather worked on the Alaskan pipeline. Five years later, the energy crisis drove them to Seattle.

Barron settled happily into the Bellevue (Wash.) School District. An avid reader and writer of short stories, she was strong in the language arts in addition to being naturally talented in math and science. Until Barron was 16, she wanted to be a novelist. That’s when Ed Ramey’s chemistry class changed her world.

As the third of 10 children in a close family, Barron found that she was somewhat “lost in the crowd” at home. So for her, school became a way to make connections with mentors. Barron received positive feedback from her teachers, and many, like Ramey, had a very strong and positive influence on her life.

“Chemistry was the most beautiful, interesting subject I’d ever studied,” recalls Barron. “I totally idolized Mr. Ramey — he had so much energy and such a love for the subject, and he even acted out how the molecules behaved.

“On the last day of class I told him I wanted to be a chemist. He said, ‘I tell you what. Don’t be a chemist. Be a chemical engineer. You’ll learn the chemistry, you’ll learn how to apply it and you’ll make a lot more money.’ Essentially I responded with a ‘Yes, sir!’ even though I didn’t know a thing about chemical engineering.”

Working 20 to 25 hours a week to put herself through school, Barron graduated cum laude in 1990 from the University of Washington with a bachelor’s degree in chemical engineering. In her senior year one of her professors encouraged her to go to graduate school. The thought hadn’t even occurred to her.

“Neither of my parents had gone to college, so I wasn’t thinking of more school,” says Barron. But off she went, to the University of California, Berkeley, to study polymers for biotechnology applications.

Four months after she arrived, her adviser left to start a biotechnology company and never came back. This turn of events gave Barron the luxury of defining her own research project. She decided to focus on the mechanism of DNA separation, a critical component of DNA sequencing. Having free rein on her research project, she decided which experiments to run, interpreted the data herself and delivered all the talks on her research, which is highly unusual for a doctoral student.

Those five intense years, Barron feels, trained her to be an independent investigator, honed her communication skills and gave her the self-confidence to become a professor.

One of her current research collaborators, Gary W. Slater, a theoretical physicist with expertise in polymer physics, remembers meeting Barron when she was still at Berkeley. Both were invited speakers at a DNA sequencing symposium.

“Her former adviser, David Soane, was scheduled to speak but was unable to come. He sent Annelise in his place,” says Slater, a professor of physics at the University of Ottawa in Canada. “She was by far the youngest speaker and certainly the most energetic. As Annelise presented data from her research, I slowly realized she was showing data that my theory couldn’t explain. In fact, what she was showing was, according to my theoretical work, impossible! This was, needless to say, a huge surprise to me.”

Slater introduced himself to Barron and explained that he was furiously taking notes and making calculations during her talk in preparation for a new paper to address this new discovery. He and Barron have been collaborating on different DNA sequencing projects since that day in 1993.

Speeding up the Sequence
Biochemist Frederick Sanger won a Nobel Prize in 1980 for a method he developed that enables scientists to read the DNA sequence contained in any genome, including the human genome. But before a sequence of chemical bases can be determined — the combinations of adenine, thymine, guanine and cytosine, or A, T, G and C, that make up genes — the DNA fragments (ranging from 10 to 700 bases each) must be separated according to size. This essential step remains difficult, slow and expensive.

“Genome science will open up new vistas that we can’t even fathom,” says Barron, who has received funding from the National Institutes of Health, the Human Genome Project and the American Cancer Society, to name a few. “And we’re not just talking about the human genome. All genomes will be important — from mice and rice to fruit flies and corn. Scientists will sequence all organisms that are of medical, environmental and consumer interest.”

Although DNA sequencing technology has progressed in recent years, it is still in its infancy, similar to where computers were in the 1970s. The Human Genome Project has taken more than 10 years and billions of dollars to produce the first working draft of the human genome in its entirety — 3 billion DNA base pairs of linear information.

Current technology separates DNA fragments using a thick, viscous solution — 100,000 times thicker than water — in which a matrix of entangled polymers acts as a molecular sieve. A strong electric field is applied to the solution, causing pieces of DNA to move like snakes through the matrix, with smaller pieces going through quickly and larger ones more slowly. This is done in bundles of 96 long glass tubes, each a little thinner than a hair.

Barron’s goal is to shrink this cumbersome technology and put it on a glass chip. But the current gels are so thick that the pressure required to load them onto a chip’s microchannels would blow most chips apart. What’s needed is a polymer solution that can be loaded easily while still performing good DNA separation.

“We worked for three years to pinpoint the desired chemical and physical properties to give us the right polymer,” says Barron, who received a 1999 Presidential Early Career Award for Scientists and Engineers from the NIH–National Human Genome Research Institute for her creative research.

“Water-hating and water-loving groups of molecules were important, and chain length was important, too. We needed the polymers to entangle, and most critically, they needed to collapse dramatically in volume at a certain temperature to be loaded onto the chip.”

With much trial and error Barron and her students produced a polymer with a “viscosity switch.” A simple change in temperature altered the polymer solution from thick to thin and back to thick again. It could be loaded onto a chip, and the technology produced DNA separation identical to those of the genome centers.

Slater, who works with Barron to analyze data from her experiments and to suggest possible next steps, can testify that Barron thrives on solving difficult problems. “Annelise’s approach to polymer engineering is far more quantitative and deeper than that of most other researchers,” he says. “Others try polymer after polymer and just drop them if they don’t work. Annelise doesn’t throw the mistakes in the garbage can. Instead, she analyzes them and tries to understand why they don’t work. She designs polymers with a plan.”

Barron now wants to improve her “viscosity switch” polymer to make it even more effective. She also is working with Slater on a radically different and higher-risk DNA separation scheme that, if successful, might even eliminate the need for entangled polymer solutions of any kind.

Commitment to Teaching
Barron also is a force to be reckoned with in the classroom.

“Professor Barron has motivated the living daylights out of me,” says David Drelicharz, a chemical engineering senior from Wilmette, Ill., who is enrolled in a rigorous all-day laboratory class taught by Barron. “I have learned a great deal about performing to expectations from her. She’s tough but in a good, constructive way.”

Barron says that her passion for research drove her to become a professor, but she has unexpectedly found joy in teaching and mentoring students. “When I first came to Northwestern, I didn’t really know what teaching undergraduates was like,” she says. “In their sophomore year our students are required to take an introductory chemical engineering class, which is boot camp for both students and assistant professors. You really have to turn on your charm and engage them with real-world examples.”

She also finds mentoring graduate students extremely rewarding. “Graduate students arrive as great raw material — bright and curious but somewhat timid about public speaking and voicing their own opinions,” says Barron. “By the time they leave, each one has become a persuasive and intelligent scientist.”

She feels it is vital to bring different opportunities to students’ attention, to point them in the direction of difficult classes or careers they hadn’t considered. “Professor Barron likes to challenge her students,” comments Stephanie Portle of Northbrook, Ill., another senior who has had Barron as an adviser. “She encouraged me to take classes that I would not otherwise have taken. She recently helped me decide to apply to graduate school, something I had been debating for a long time. She obviously cares about us.”

Barron often describes her own journey to students, explaining why she is in the field. She thrives on hectic but stimulating days that can include advising students and overseeing research, meeting with colleagues, writing grant proposals, teaching classes, fielding phone calls and e-mail messages and trying to get home at a reasonable hour.

But what if she were not a chemical engineering professor?

“I’d love to write,” says Barron. “And to garden and spend more time taking care of my son. But I have been extraordinarily fortunate because this is a wonderfully flexible job for having a family. Research is on my mind during all my waking hours, and I’m making connections between disparate things. I can dream where I want to go. It’s intoxicating.”

Megan Fellman is a senior editor in the Department of University Relations. She covers the sciences and engineering for the media relations group.

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