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University lab discovers fascinating new ion channel

By Iona Feldman

Section: News

October 4, 2013

Professor Christopher Miller (BCHM) co-authored a paper on the structure of a newly discovered fluoride-exporting ion channel. This channel, which removes ions toxic to certain microorganisms, has a particularly unique structure that fascinates scientists. Meanwhile, as Professor Miller is out of the country, students at Brandeis conduct research in his lab on fluoride carriers.

The paper, which was written with postdoctoral research students Randy B. Stockbridge, Janice L. Robertson and Ludmila Kolmakova-Partensky, was published in the scientific journal eLife at the end of August.

Professor Miller, currently on a seven-month sabbatical in England, gave some insight into its themes in an email exchange earlier this week. Although he draws no final conclusions about their practical use, Miller noted the scientific value of the fluoride-exporter channels for their own sake. “Their real interest lies in their very unusual chemistry,” he said, a chemistry that differs in shape from all other channel proteins discovered in the past.

In addition to researching fluoride-exporting channels, Miller’s lab at Brandeis also looks into fluoride transporters. Although these proteins perform a very similar function, their study involves biochemical research that is fundamentally different from that which goes into studying channels. Students explained this research, including Ashley Brammer, a fifth-year graduate student in the biochemistry program, and Lily Ji ’14, who majors in HSSP and Business and is also a biochemistry MSBS candidate. Both have done research in the area of fluoride transporters while working in Miller’s Lab.

Brammer focuses on the fluoride pumps that actively remove fluoride from inside cells. The transporters, also known as antiporters because they move different ions in opposite directions, were first discovered at Yale University.

“My involvement has been basically to characterize this protein from the bottom up,” Brammer said. “It’s a brand new protein. No one has ever looked at it before.”

Because the protein in question came from a family that also exports chloride, Brammer worked to discover if this protein also exports chloride. She and her colleagues found that it does but not as well as it does with fluoride. These properties may be attributed to the protein’s selectivity, and another task of the researchers has been to understand how this selectivity works.

Ji’s research focuses on the mechanism that allows these bacteria to resist fluoride poisoning. She works in an artificial environment to best observe its effects and concluded that despite the bacteria’s overall ability to survive in fluoride environment of 100 micromolars, it grows much faster when it has the correct transporter protein to remove the fluoride. Ji also studies how bacteria take in fluoride, leading to the crisis from which they need to be saved in order to survive.

Brammer, Ji and their fellow researchers use a variety of tools to collect data. A key focus of this is the molecular biological methods that manipulate cells to change just one part of the protein. The researchers use E. coli to overexpress the proteins that they study, later removing bacteria from the cells. The proteins are then examined in an artificial fat environment. Researchers can properly examine the proteins only in such places because membrane proteins do not fold and function well in water environments. This is one of the primary challenges faced in a lab that specializes in membrane proteins. The research also depends heavily on crystallography, which is significantly more difficult to do with membrane proteins. Through the use of these diverse techniques, the lab aims to understand the structure and function of membrane proteins.

For anyone interested in getting involved in biological research on campus, Brammer and Ji offer advice. As an undergraduate, Brammer did research in organic chemistry and decided to change directions in graduate school toward biochemistry. She recommends that graduate students doing research rotations in their first year should try to diversify them, to test out labs of varying sizes and areas of this. She believes that this is one of the best ways to determine where they would work best in the future.

Ji has some suggestions for undergraduates looking to excel in fields such as this.
Coming to Brandeis for its pre-health track, Ji took organic chemistry and physics as a first-year. “Take these higher-level core courses early on. Take the risks. You’ll be freeing up more of your time and opportunities to do more things that you’ll like in the future.”

Ji also became involved with research by approaching Miller and inquiring about different opportunities. Although students may also apply to posted positions, Ji made the first move and spoke to Miller before a position appeared. A proactive attitude will reveal some excellent opportunities available on campus.

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