FYI Research:
Water and protein: building blocks of publication for chemistry major

If you're not a scientist, you might think you know a lot about water. You cook with it. You bathe in it. You try to drink eight glasses of it every day.

But at a molecular level, said Joseph Batchelor, scientists are still struggling to understand water's structure. It's complicated. "Water kind of flickers in and out of an icelike, hexagonal structure and a liquid structure," Batchelor said. "It's an ensemble of different states, and it fluctuates very rapidly." Things get even more complicated when you look at how other substances affect water.

Batchelor, a senior chemistry major at Carolina, recently did experiments that overturned a long-held idea about the relationships among certain solutes (substances dissolved in water), water structure and protein stability. These experiments, conducted under the supervision of chemistry professor Gary Pielak, resulted in a paper -- Batchelor's first -- published in February in the "Journal of the American Chemical Society."

Pielak had wanted to study these relationships for four or five years. "The function of a protein depends on it having a certain structure," Pielak said. "When you add heat, that structure goes away, and so does its function." The more heat necessary to break down the protein, the more stable the protein is considered. Certain compounds, dissolved in water, are known to increase or decrease protein stability. No one knew exactly how this process worked, but many scientists believed for decades that solutes indirectly affected proteins by changing the structure of water in the solution. No systematic experiments had tested this belief.

Alina Olteanu, a graduate student in Pielak's lab, did preliminary work that showed what Pielak wanted to do was possible. Then she had to focus on her dissertation, a separate project. Pielak turned to Batchelor, with whom he had worked on an earlier project. "It was a great project for Joe, because it was both chemical and mathematical," Pielak said.

Batchelor's experiments used Carolina's pressure perturbation calorimetry instrument (PPC), one of the few such instruments in the world, which can collect large amounts of data quickly. Batchelor studied how known protein stabilizers and destabilizers changed the structure of water by measuring changes in heat when bursts of heat and pressure were applied. He and Pielak thought they would see a correlation between when compounds made or broke the water's structure and when they stabilized or destabilized proteins.

They didn't find what they expected. After two months of experiments, Batchelor's results showed that whether or not a solute affected the water's structure had no correlation to whether or not it made proteins more stable. Their research shows just how elusive water can be, the researchers said. "We don't understand the liquid we encounter most often," Pielak said. The researchers now suspect a solute's protein-stabilizing or destabilizing qualities may have to do with other factors such as the solute's affinity for the protein itself or how much volume the solution occupies.

Pielak said research such as theirs could potentially apply to compounds that can make protein-based pharmaceuticals more stable. And Batchelor said the applications are even broader. "Proteins do everything in the cell," Batchelor said. "This work leads to a better understanding of how they function with different compounds."

While interviewing at graduate schools this spring, Batchelor enjoyed discussing his paper with prospective colleagues. A faculty member at one school was about to publish a paper of her own that related solute's effects on proteins to their effects on water. "I was kind of afraid she would be mad at me," Batchelor said. "But it was fun talking with her, because we both agreed that no one really knew what was going on, it was really complicated and people need to think about it more."

After his graduation from Carolina next month, Batchelor will pursue graduate work at the University of California at Berkeley. Before he leaves, he is training a new undergraduate, freshman Michelle Mian, to continue work with Pielak. She has just learned that the Smallwood Foundation will fund her research this summer.

Batchelor is lead author of the paper. Co-authors are Pielak, Olteanu and Ashutosh Tripathy, director of Carolina's Macromolecular Interaction Facility, which houses the PPC. The National Science Foundation and the Smallwood Foundation supported the study.

Provided by Research and Economic Development.
Editor: Neil Caudle. Writer: Michelle Coppedge.

Technology transfer update

The Office of Technology Development helps Carolina faculty, students and staff develop and commercialize patentable inventions resulting from their research. In March 2004, the University executed four license agreements and had four U.S. patents issued.

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