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Small molecules, big opportunities

New faculty appointment to bring novel technology to Salk

On July 1, when Salk's newest faculty member member, Alan Saghatelian, officially joins the Clayton Foundation Laboratories for Peptide Biology, the Institute will not only gain considerable expertise in metabolite and peptide profiling; it will also gain access to his innovative technique for analyzing these small molecules. The result will almost certainly be numerous cross-disciplinary collaborations that promise to advance our knowledge of metabolism and help identify potential therapeutic targets for a host of diseases.

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Alan Saghatelian

Saghatelian, currently an associate professor of chemistry at Harvard, was first bit by the research bug two decades ago, while studying chemistry at UCLA. After working in an organic chemistry professor's lab for a few years, however, he was ready for something new following graduation. Intrigued by the intersection of chemistry and biology, he entered the graduate program at The Scripps Research Institute, where he concentrated on the synthesis of peptides capable of carrying out chemical reactions.

"It was a really important decision, even though I didn't realize how important," he says. "One of the things I liked about TSRI was that it was different from traditional chemistry departments. People were trying risky things, and I felt it would be a great opportunity to learn. And although my graduate research focused on biochemistry, I realized that I found problems in biology more interesting."

After earning his Ph.D. in 2002, Saghatelian remained at TSRI four more years as a postdoc, developing a novel technology to identify metabolites. "Being an organic chemist, I was very interested in small molecules," he explains. "Metabolites are a group of molecules that aren't usually analyzed. We know a lot about proteins in many diseases, but we don't know if metabolites are involved at all or if so, which ones."

Metabolites and peptides have vital roles in human physiology and disease. The peptide hormone insulin, for example, controls physiological levels of the metabolite glucose, and the aberrant signaling of either leads to diabetes. But to understand their function and regulation, it is necessary to detect and quantify these molecules under different biological conditions, such as identifying changes in them during disease. Unfortunately, a dearth of available experimental tools has made it difficult to study them. Part of the problem, Saghatelian says, is that the tools that are normally used to measure gene and protein levels completely miss metabolites. So for his own work, he turned instead to mass spectrometry, leveraging its capabilities to glean the information he needed. "If you're looking at lots of small molecules, it's the best way to tell what's going on," he says.

At Harvard, Saghatelian continued his research and expanded his focus to include bioactive peptides, such as hormones, to understand their regulation. Among the breakthroughs his technique produced was the discovery of a new metabolite that may have an impact on diabetes.

Despite this progress, in recent years, he had begun to feel the need for collaborations with biologists to take his research to the next level. "If I detect that a molecule is changing, I have some ideas of what is important and what to do with it," he says. "But it's also really helpful to talk with somebody who has done this before and who can tell me which model to look at or refer me to people who can get me the best samples to analyze and tell me what I should be looking for."

Because his interests are much more in line with those of Salk scientists, and because Salk is structured without departments and silos, when the opportunity to move his lab to the Institute came up, Saghatelian jumped at the chance. "Salk offers a unique opportunity for me to integrate with some of the world's best biologists," he says. "I think it will push me to be a better biologist and push the research forward by showing the full scope of its power to make discoveries that can impact medicine."