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Moving Mass Spec Along

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Paola Picotti
Title: Senior Research Fellow, Institute of Molecular Systems Biology, ETH Zurich
Education: PhD, University of Padua, 2006
Recommended by: Ruedi Aebersold

Paola Picotti is one proteomics pioneer set on bringing the field into the 21st century. In the last year, Picotti has been hard at work developing a brand new generation of proteomics technology that she hopes will serve as an alternative to shotgun proteomics. This is a novel, targeted proteomics approach, based on the mass spectrometry technique called selected reaction monitoring or multiple reaction monitoring. "The choice of this approach is based on the fact that it consists of the generation of mass spectrometic assays that are very sensitive and highly specific which you can use to detect and accurately quantify a given protein or a set of proteins of interest. And this can be done across many samples in a fast and reproducible way," Picotti says. "In the last few years, I was focused on developing the technical aspects of this new approach, and on testing it and demonstrating that it works by bringing it to a point where it can be broadly applied to any set of proteins."

Picotti began her proteomics journey during her graduate studies at the University of Padua, where she studied protein chemistry, including protein folding and misfolding, and the stability of single proteins. But it was when she joined Ruedi Aebersold's lab in 2007 to pursue her postdoc fellowship that she found herself in a position to work on the cutting edge of proteomic tool development and address the limitations of the standard shotgun approach.

"It's a great environment in Ruedi's lab because you can experience a high degree of creative freedom, but still you have the possibility to validate and improve your work as well as interact with a huge team of colleagues from different fields that are part of Ruedi's group," she says. "I also learned to go beyond just doing some incremental research and to think about the needs of the field right now, and whether the current technology is fulfilling them and to somehow be brave enough to try alternative approaches and change directions. It might fail, but if it works, you're rewarded."

Looking ahead

In the not-so-distant future, Picotti would like to see proteomic technology refined to the point where it can be applied to single cells and day-to-day work, both in the laboratory and in clinical settings. "I could certainly imagine that there will be a steady increase in the sensitivity of the mass spectrometers that is continuously pushed by the vendors, and this will probably allow us to detect down to the lowest abundant proteins in a human cell, and also in human body fluids, which are even more complex," she says. "Hopefully proteomics could be applied to single cells and not only to average behaviors of cell populations. Maybe also proteomics will finally reach a broader application to everyday lab life and clinics."

Publications of note

In August, Picotti and her colleagues published a paper in Cell entitled "Full dynamic range proteome analysis of S. cerevisiae by targeted proteomics." She described this paper as a proof-of-principle study that showed that the targeted proteomic approach she is helping to develop is a fast, simple, and economical way of exploring the dynamics of cellular pathways.

And the Nobel goes to...

Picotti says that if a trip to Sweden is in the works for her somewhere down the line, she'd like it to be for developing "a clear logic process or some step-by-step approximation to the solution of a problem, something driven by an intellectual process rather than a discovery by chance," she says. "Although we know that luck and chance always play some important role in advancing science."

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