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Mass Spec, But Better

  • Title: Assistant Professor of Chemistry, University of Wisconsin
  • Education: PhD, University of Florida, 2002; Postdoctoral position, University of Virginia, Don Hunt's lab
  • Recommended by: Steven Carr, David Muddiman

In some circles, it's probably enough to say that Joshua Coon did his postdoc in Don Hunt's lab to illustrate the potential of this young mass spectrometry expert-in-the-making. But for everyone else (not to mention for the sake of filling this page), some elaboration is in order.

Coon, who set up his lab at the University of Wisconsin about a year ago, is looking to make waves in the proteomics community. To be fair, he's already started that thanks to his work on a technique known as electron transfer dissociation, or ETD. He was involved in that project with John Syka, another UVA scientist, while in Hunt's lab — and since then, the novel ion fragmentation technology has been exclusively licensed to Thermo Electron.

The goal of ETD, and the big need for proteomic scientists in general, is to enable the analysis of larger peptides or even whole proteins by systematically breaking them up at specific sites in the protein. “There's a pretty big limitation in current proteomic technology,” says Coon: modern proteomic tools chop proteins into such tiny fragments that their context in the original protein is lost. That means larger motifs, such as peptide or protein patterns and alternative splicing, are “for the most part invisible right now,” Coon says. As many as three-fourths of all proteins are expected to have a splice variant, and many proteins will have several splice variants, he adds. But a single peptide under analysis in a mass spec is likely to be common to all splice variants, so today scientists can't tell the various protein personalities apart. “This is the level of detail that is missing from today's proteomic analysis,” Coon says. “What is the context [of these peptides]?” To that end, Coon's lab will be busy “working on new tools that will analyze large peptides or even whole proteins,” giving scientists “a better chance [to] detect very relevant events,” he says.

But technology development won't happen in a vacuum in Coon's lab, where proteomic work in developmental and stem cell biology represents the applied half of his projects. Coon's team is collaborating with other Wisconsin scientists to analyze the proteomic changes that take place when, for instance, “an embryonic stem cell commits to differentiate and goes into a specific lineage,” he says. Understanding post-translational modification patterns and fleshing out the signaling pathways in stem cells will be top priorities.

Looking ahead

Traditional proteomics is simply not going to allow scientists to understand exactly what proteins are doing and how they're doing it, Coon says. The ideal technology for this field would have “the capability to characterize all proteins from a biological sample in their intact form, and … do that with a dynamic range of 109,” he says. It's only with that kind of dynamic range that researchers will be able to “see the very abundant things and the single-copy-per-cell things,” he adds, noting that being able to study intact proteins will be an essential step for scientists in this discipline. “That's not easy,” he says. “That's the next frontier.”

Publications of note

The best way to get a good idea of what Coon will be up to is to read “Advancing proteomics with ion/ion chemistry,” a review he wrote for BioTechniques (June 2006). “It's intended for a wide audience,” Coon says, “and describes my vision.”

And the Nobel goes to…

Coon knows that no matter how interesting technology development is, it's not the ultimate goal of all this work. That's why he says he'd like to accept the Nobel for “a key contribution to understanding developmental biology and stem cell differentiation and lineage commitment.”

The Scan

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'Poo-Bank' Proposal

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Spurred to Develop Again

New Scientist reports that researchers may have uncovered why about 60 percent of in vitro fertilization embryos stop developing.

Science Papers Examine Breast Milk Cell Populations, Cerebral Cortex Cellular Diversity, Micronesia Population History

In Science this week: unique cell populations found within breast milk, 100 transcriptionally distinct cell populations uncovered in the cerebral cortex, and more.