Walton Discovers New Genes

Durham, N.C. (October 2006) – Although Cryptococcus neoformans can make people sick, to Felicia Walton the fungus is also a work of art when captured in a through-the-microscope image. 

In one image, the cell walls of a malformed strain of the fungus glow bright blue when stained with a dye called calcoflour white, and its cellular nucleii shine emerald when stained with a dye called sytox green. 

"Looking at something as stunning as that and being able to gain some kind of insight from it is one of the reasons I'm studying biology -- the visual aspect," said Walton, a Trinity College senior. 

"It was just very beautiful to look at," agreed Alexander Idnurm, a postdoctoral researcher who has worked closely with Walton in the Department of Molecular Genetics and Microbiology for the nearly three years since she arrived there as a first-year undergraduate with no research experience. "Those particular strains were very striking in terms of their morphology." 

The editors of the research journal Molecular Biology of the Cell also were impressed, placing Walton's fungal portrait on the cover of their September issue. 

Walton also was first author of a report in the issue on these and other oddly elongated Cryptococcus cells. Her co-authors were Idnurm and Joseph Heitman, director of the Duke Center for Microbial Pathogenesis and head of the lab in which Walton works. 

This was the second scientific paper Walton has co-published with Idnurm and Heitman in respected journals since coming to Duke from her home in Asheville, N.C. "Some graduate students don't publish anything before they get their degrees," Idnurm said. "This is the equivalent of research as a Ph.D. or a postdoc." 

"Felicia has matured into a full-fledged contributing member of our research group," Heitman said. "This is no small task for an undergraduate working in a group of a dozen postdocs and four or five graduate students. Even amongst this talented group, Felicia stands out with her ability, her questions and her productivity." 

To do the work described in her latest journal article, Walton created a genetic library of about 50,000 abnormal forms of Cryptococcus and then looked for strains whose cells could no longer properly divide. 

Her paper zeroed in on six genes and associated proteins that caused the normally round cells to form stretched-out shapes. That information could help researchers develop ways to disable the fungus, which can cause life-threatening infections in the nervous systems of patients with compromised immune systems. 

In earlier work, Walton investigated how Cryptococcus produced protective coatings of the pigment melanin to help maintain its pathogenic potency. Then she cultured thousands of different strains of the fungus on laboratory petri dishes, looking for mutant forms -- and their associated genes -- that could no longer properly make melanin. 

"At the time, the whole field of Cryptococcus research knew of only two or three genes involved in that process," Idnurm said. "Felicia managed to find another six genes. It was an incredible achievement -- like doubling the current research knowledge. 

"And to do that when working only part time while not in classes, and then give up summers to do more research, it was amazing she could be that productive," he said. 

Walton has had an interest in science and biology "for as long as I can remember," said the graduate of Asheville's T. C. Roberson High School. 

She also had parents "who convinced me that I could do whatever I set my mind to," she added. Her mother is employed by a nonprofit group that works with families battling illnesses and disabilities, while her father works in medical computer support. 

"So I didn't feel intimidated when I came to Duke, because I felt I could make an impact and make a difference," she said. 

Hitting the ground running, she entered Duke's signature FOCUS program, which provides first-year students with opportunities to attend interdisciplinary seminars with leading researchers clustered around a common theme. 

"I thought for a time I would be a physicist, but I really loved the idea of studying life at the molecular level, because I think it's just tremendously beautiful," she recalled. Choosing a FOCUS program in biotechnology, she also began talking with professors about doing research in their labs, and was surprised by their encouragement. 

Heitman's group, which explores the genetic and biochemical factors behind the virulence of Cryptococcus, as well as strategies for disabling the fungus, particularly captured her interest. "Joe also had this track record of wanting to have undergraduates working meaningfully in his lab," she said of Heitman. 

"When I first approached him, I just wanted to get my foot in the door," she said. "He told me that I was going to start doing real research, right away, just headfirst." 

Heitman was right. 

Walton started by learning to culture fungus, identify genes and proteins, use a bacterium as a syringe to inject genes into microorganisms, squint endlessly into a microscope counting and characterizing cells -- and expect disappointments. 

"I've always been determined and self-motivated, and that's certainly something that helps as a scientist," she acknowledged, "because there are a lot of setbacks and failures that you have to keep pushing through." 

Walton's efforts have been supported by a series of undergraduate research funding grants, including one from the Howard Hughes Medical Institute and another from the American Society for Microbiology, during academic years as well as summers. 

In the process, she has learned the value of having strong mentors. "Alex is patient, and he probably is the best teacher I have had at Duke," Walton said of Idnurm. "I've learned more through research than in my classes," she added, "and you learn in such a different way." 

Idnurm, in turn, is sold on the value of having undergrads in the lab. "I think they're more willing to question established dogma, dogma that is probably wrong," he said. "They're not politically wise enough to toe the party line. We'll say, 'This is the way it is.' They'll say, 'Why is that?' And we often we start thinking, 'Well, maybe you're right, and we're probably wrong about that.' 

"They bring fresh ideas to the lab, and it's also nice to teach new students your methods and benefit from their enthusiasm," he said. "I know I definitely become a lot less jaded because of that." 

"We have very high expectations for the undergraduates who conduct research in the lab, and Felicia has exceeded all of them," added Heitman. "We look forward to witnessing the next stages of her career development beyond Duke." 

Walton, a double major in biology and chemistry who also finds time to pursue an array of other subjects, plans to pursue a Ph.D. She has been nominated for several graduate scholarships to study abroad.

Contact: Monte Basgall

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Senior Gets Research on Cells Published

Durham, N.C. (October 2006) Lots of little kids ask how things work. Felicia Walton asked how a cell divided.

Walton, now a senior, maintained her scientific curiosity, and her latest research on an infectious fungus was published September in the research journal Molecular Biology of the Cell.

The paper was co-authored by Dr. Joseph Heitman, professor of molecular genetics and microbiology and director of the Center for Microbial Pathogenesis, and Alexander Idnurm, postdoctoral research associate.

Walton studied images of the disrupted pattern of cell division in the fungal pathogen Cryptococcus neoformans to identify proteins crucial to the infectious organism's ability to resist certain drugs.

"The idea is that perhaps we can find a drug that can target these proteins and inhibit their activity," Walton said.

The research could help develop ways to combat Cryptococcus, which infects people with compromised immune systems, such as chemotherapy or organ transplant patients.

"Cryptococcus is a major problem in Africa and other subtropical regions because it infects many AIDS patients," Walton said.

Her findings also greatly increased the current research on the genes involved with the chemical melanin-a pigment that helps the pathogen evade immune systems.

This is the second scientific paper Walton has published since beginning research as a freshman, Heitman said.

Walton began her Duke career by participating in the biotechnology-related Focus program.

With a professor's encouragement, she contacted Heitman and soon began researching with him.

"I thought, 'Oh my gosh! I've never had any research experience before and they're not going to want to talk to me,'" Walton said.

Instead, she found Heitman's lab a tremendous support system, especially for undergraduates.

Heitman said Walton was "pretty extraordinary," and added that he welcomed the chance to work with undergraduates.

"She performs at the level of a grad student and a post doc," Heitman said.

Walton's research began with a chance discovery of an abnormal strain of Cryptococcus neoformans.

"It started with just a very innocent observation of a really cool-looking strain which was very different than what we were used to seeing under the microscope," she said.

Heitman said he, Walton and Idnurm were happily surprised to learn that an image of the strain would be on the journal's cover.

"I think it's even more stunning to think about aesthetic beauty of the picture when you understand the genetics and he science behind it," Walton said.

Contact: Cosette Wong