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Mann Leads the Charge of Mass Spectrometrists into Proteomics

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AT A GLANCE

Name: Matthias Mann

Age: 42

Position: Professor in the Department of Molecular Biology, University of Southern Denmark, and Chief Proteomics Officer, MDS Proteomics

Prior Experience: Developed nanospray ionization, the peptide sequence tag method for identifying proteins using tandem mass spectrometry, and founded Protana, later acquired by MDS Proteomics

Like many scientists who ended up in what has come to be known as proteomics, Matthias Mann wasn’t always a biologist. In fact, he studied physics as an undergraduate and earned a master’s degree at the Max Planck Institute for Fluids Research in Göttingen, Germany, for his work applying mass spectrometry to physical chemistry.

But it was while at Max Planck that Mann met John Fenn, an analytical chemist at Yale University who was developing new mass spectrometry techniques and applying them to fields outside the physical sciences. Mann followed Fenn to Yale, where he spent the years between 1985 and 1988 helping Fenn develop the electrospray ionization technique and use it to weigh proteins.

“At the time you couldn’t analyze proteins by mass spectrometry readily,” he said. “That was the first step, and then I went more and more into the actual biological applications. Also it was pretty apparent that this would be a revolution in protein analysis, so I wanted to stick with it.”

Mann has certainly not wavered in his dedication to protein analysis since then. After leaving Yale — but not before meeting his future wife, a Dane — he moved north of his native Germany to Denmark, joining Peter Roepstorff’s lab at the University of Southern Denmark, in Odense. There, he expanded on his graduate work by using electrospray mass spectrometry to identify the amino acid sequence of recombinant proteins, something no one had attempted before. Mann also contributed to the development of peptide mass fingerprinting while in Odense, a technique for using MALDI-TOF mass spectrometry data to identify proteins.

However, it wasn’t until Mann took a research position at the European Molecular Biology Laboratory in Heidelberg, that he truly came into his own as a protein mass spectrometrist. During the 1990s he developed a slew of experimental methods that others have widely adopted, including nanoelectrospray ionization with his graduate student Matthias Wilm, a technique for using partial MS/MS sequence data to identify proteins called peptide sequence tagging, and other algorithms for matching MS/MS sequence data with their corresponding amino acid sequences in databases. In addition, he laid the groundwork for the analysis of multiprotein complexes by mass spectrometry, and in 1996 he published the first large-scale study of proteins in yeast. The 150 he identified were “quite a large number at the time,” he said.

Mann particularly enjoyed working at EMBL because it granted even entry-level scientists the resources to build their own independent research groups — a rarity in Europe. At the same time, the laboratory’s emphasis on solving molecular biology problems helped Mann focus his mass spectrometry work. “Because I was at EMBL we [knew that] if this was to be useful in molecular biology, it was clear that you had to reach [a certain level of sensitivity]. Otherwise people would still use Edman sequencing.”

Towards the end of his tenure at EMBL, Mann and one of his post-docs, Ole Vorm, began receiving requests for nanospray equipment from other researchers. The EMBL machine shop, however, couldn’t build the small nozzles and their associated electronics fast enough, (nor did they want to, said Mann). When Mann accepted a teaching position at the University of Southern Denmark — partly to be closer to his wife — he and Vorm decided to start a company, and named it Protana, as a contraction for the Protein Analysis Company, to build and sell nanoelectrospray equipment.

Mann and Vorm also realized that other companies would pay them to perform research on protein samples using the techniques developed at EMBL. They bought a Thermo Finnigan LCQ ion trap mass spectrometer, and soon attracted the attention of MDS, a Canadian medical research service and equipment company that took an early equity stake in Protana. “We knew [MDS] because they own Sciex, and had worked with them at EMBL,” said Mann. “They independently got the idea that proteomics was a hot area and wanted to get involved.”

MDS had also invested in a startup out of Tony Pawson’s lab at the University of Toronto, and in the summer of 2000 decided to merge the two into MDS Proteomics. Despite having to relinquish some control of the company, Mann went along with the plan because it meant he could apply Protana’s technology on a much larger scale, with the potential for addressing human disease. “We could have continued as just Protana but we were a little more service-based,” Mann said. “You must do that for a long time to grow into a big operation — to have a big splash.”

Today Mann works at MDS Proteomics as chief proteomics officer, and Vorm as senior vice president and managing director for Europe. The company’s Odense location is smaller than the recently opened proteomics megacenter in Toronto, but Mann says his Danish group is actively involved in the company’s drug discovery efforts with Abgenix, its pharmaceutical partner. “What we’re doing here, particularly in Denmark, is looking at cell surface proteins in diseases such as cancer and try to find what’s differentially regulated, or just different on the cell surface that can then be a drug target.”

But despite his involvement with the company, Mann still spends most of his time in his academic lab, which MDS Proteomics supports in return for a “right of first refusal” to commercialize the technology. His most recent work involves subfractionating cells to study the proteins in the nucleolus, and additional mass spectrometry development using his lab’s QSTAR spectrometer from Applied Biosystems and MDS Sciex. (The Journal of Proteome Research published Mann’s most recent paper on MALDI tandem mass spectrometry on its website on Jan. 18.)

Mann has also volunteered his time to lead a HUPO committee to identify informatics issues in proteomics and develop educational seminars for other researchers in the field. He wanted to participate, he said, because there is great need for an organization that can set data quality standards, as well as bring scientists together from all corners of the proteomics globe. “There are these traditional proteomics people [in HUPO] and then there are other people who are more based on these new methods like mass spectrometry, and that needs to be reconciled as well,” he said. “I’m of course heavily biased towards mass spectrometry!”

— JSM