Abstract

BioTechniquesVol. 39, No. 3 ScientistsOpen AccessProfile of John Yates III, Ph.D.Professor of Cell Biology and head of the Proteomic Mass Spectrometry Lab, The Scripps Research Institute, La Jolla, CALaura BonettaLaura BonettaSearch for more papers by this authorPublished Online:30 May 2018https://doi.org/10.2144/05393SP01AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit Getting SidetrackedWhen I started my undergraduate studies at the University of Maine, I was thinking about going to medical school. I had injured my leg playing football in high school and became interested in medicine while I was convalescing in the hospital. But I was eventually sidetracked by the biology and chemistry courses I took. Given the state of medical finances these days, I am glad things turned out the way they did.I got my first taste of mass spectrometry during an undergraduate chemistry course. Right away, I thought that the technique was the future—mostly because the instrument had a computer attached to it. To me, that was so cool. I guess I had the right insight, if not necessarily for the right reasons.I decided to do my graduate work at the University of Virginia in a mass spectrometry lab. We were developing and applying tandem mass spectrometry to the sequence analysis of proteins. At that time, it would take a year just to sequence one protein. Twenty years later, mass spectrometry is able to tackle much more complex questions.What appeals to me are technically difficult problems. One of my favorite papers was the one we published in Nature in 2002 on the proteome of the malaria pathogen, Plasmodium falciparum. The study identified more than 2400 proteins.Daniel Carucci, formerly of the Naval Medical Research Center, and one of the people who had gotten the malaria genome project off the ground, had heard me give a talk about my work identifying complex mixtures of proteins in different systems. He asked me, “Could what you talked about work with malaria?”It was a tough problem, because you can never isolate pure Plasmodium proteins. With the life cycle of the parasite, you always get a high background of mosquito or human components. Therefore, we had to spend a lot of time working on strategies to distinguish among different proteins, and we had to do this while the Plasmodium genome sequence was being completed. There were many technical challenges to sort through, but that was part of the attraction.I was also drawn to the project because malaria is such a huge problem in terms of the number of people who are affected by the disease. I tend to gravitate toward issues that affect the developing world.In my mind, the development of the SEQUEST algorithm for correlating tandem mass spectrometry data to protein sequences was a critical step in enabling us to do the things we are doing today. When I started with mass spectrometry, a major bottleneck was throughput of data analysis. You could not do any large-scale projects. SEQUEST, which I developed about 12 years ago when I was a faculty member at the University of Washington, allowed us to take protein mixtures in solution or from cell lysates and obtain a fairly accurate identification of the proteins in the mix.Because of the patent arrangements with the University of Washington, SEQUEST is now distributed through a company. But we have developed other programs that are freely available. We spend a fair amount of time supporting people who use our software. Support is a lot of work, but I believe that if you write software, you need to take responsibility for it.The applications of mass spectrometry have changed a lot over the years, and my knowledge has gotten a lot broader to keep up with these changes. But you know what they say about generalists: you end up knowing nothing about everything.I currently have about 20 people working with me, and most are postdocs. Chemists, computer scientists, physicists, and biologists work side-by-side in my lab. It is to their advantage to have access to all these different kinds of expertise. For example, if one of the biologists is having problems with statistical analysis, he or she can ask one of the people with a strong mathematical background for help.I enjoy being the head of the lab. It is a bit like having a small business—making decisions, setting direction, taking responsibility for what happens. All these things appeal to me. Outside of work, most of what I do revolves around the lives of my three sons. It means I spend a lot of time at baseball games.FiguresReferencesRelatedDetails Vol. 39, No. 3 Follow us on social media for the latest updates Metrics History Published online 30 May 2018 Published in print September 2005 Information© 2005 Author(s)PDF download

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