Thinking Small -- Sunney Xie is interested in the molecule as an individual

December 16, 1999

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By Alvin Powell
Gazette Staff

Chemistry Professor Sunney Xie developed a technique using lasers to image biomolecules. Photo by Kris Snibbe.

Sunney Xie is devising new ways to see what few have seen before: some of the smallest building blocks of matter, individual molecules.

Using laser beams and natural fluorescence, Xie has brought new experimental techniques to Harvard, techniques he hopes can be used to better understand biomolecules – which are commonly found in living things – and biological processes.

Xie, who was named professor of chemistry last January, is one of the world’s leading researchers in molecular imaging and in single-molecule reactions.

Xie’s work is being conducted along two main tracks. On one, he has devised a way to use laser beams to see collections of protein molecules.

The new imaging method is important not because people have never seen structures of protein molecules before, but because Xie’s method allows researchers to see how biomolecules are assembled in biological membranes and how their relative position may affect their behavior.

Xie, for example, works with membranes that carry out the process of photosynthesis. By seeing the arrangement of proteins in the photosynthetic membrane, researchers may be better able to determine how the membrane converts sunlight to chemical energy.

"He’s pioneered the application of single molecule detection at room temperature, which has opened it up to biological systems," said James Anderson, Philip S. Weld Professor of Atmospheric Chemistry and chair of the Department of Chemistry and Chemical Biology. "He has a magnificent combination of scientific talent and is truly one of the warmest and most personable people I’ve met."

On the other research track, Xie is using the natural fluorescence given off by an enzyme molecule as it catalyzes chemical reactions repeatedly. A catalyst is a substance that promotes a reaction, but is unchanged at the end and so can be used again and again.

By observing the flashes of fluorescence given off by the enzyme molecule, Xie can see each time a reaction occurs.

By gathering data and using statistical analysis, Xie is learning how the same reaction varies among individual molecules of the same enzyme.

"Sunney’s work on the reactions of single [molecules] is pioneering and provides a new and extraordinarily powerful approach to understanding the complex reactivity of chemical and biological processes," said Hyman Professor of Chemistry Charles Lieber.

Understanding reactions of single molecules is an important way to gain new insight about chemical reactions, Xie said.

Even though scientists think about chemical reactions in terms of single molecules, most experiments involve large numbers of them. Watching many molecules at once has limited scientists’ understanding of chemical activity because of the potentially different actions of individual molecules.

"When you have complex molecules, such as biomolecules, seemingly identical molecules have different characteristics, their own personalities, in a time-dependent way," Xie said.

A study of an enzyme called cholesterol oxidase – which causes cholesterol to undergo a common chemical change called oxidation – shows that individual reactions don’t happen at the same speed.

Instead, the reaction speed varies as the shape of the enzyme molecule changes over time.

"The rate of the chemical reaction is slowly fluctuating," Xie said. "What we’ve shown in the past few years is that the single molecule approach has really allowed us to extract new information not apparent in large volumes of molecules."

Xie hopes that studying individual molecules will help researchers investigate subtle differences in molecular interaction and chemical activity, which could prove useful in creating new drugs or treatments for disease, Xie said.

Son of Chemists
Xie came to Harvard from his post as chief scientist for the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Laboratory, where he began his work on single-molecule reactions. Xie also served as adjunct professor of physics at Portland State University in Portland, Ore.

Xie, 37, was born in Beijing, the son of two chemists, both professors at Peking University. With chemists as parents, Xie said it seemed a natural choice for him to enter the field. Xie must have become comfortable in the company of chemists because his wife, Lin Song, is also a chemist.

He received a bachelor’s degree in chemistry from Beijing University in 1984 and then came to the United States to further his studies. He received a doctorate in chemistry in 1990 from the University of California at San Diego.

After leaving San Diego, Xie went to the University of Chicago, where he did two years of postdoctoral work.

In 1992, he became a senior research scientist in the Environmental Molecular Sciences Laboratory, a post he held until 1995, when he became chief scientist there.

Xie, whom Lieber described as an "extremely warm individual and a wonderful, caring colleague" said he is excited to be at Harvard. Xie said he is looking forward to teaching Harvard students and working with them to take single molecule and imaging work to the next level. Growing up in a house headed by two chemistry professors, Xie said he has always been fond of the academic lifestyle.

Xie has published many articles and spoken at numerous conferences and universities. He is on the editorial boards of three scientific journals. In 1996, Xie’s work on single-molecule spectroscopy won him the Coblentz Award, which is given each year to an outstanding molecular spectroscopist under the age of 36, by the Coblentz Society.