Promising ideas

This interview was published by Front Line Genomics: “A Scientist’s Work Should be Understandable for the Wider Community

 

What are you working on right now?

In terms of technology development, we are evolving our approach to Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS) to significantly enhance the throughput and the accuracy of quantifying thousands of proteins in single mammalian cells. We are also building upon and extending our ideas to enable quantifying post-translational modifications in single cells. These new types of data have motivated us to think about the conceptual framework within which we can understand them and apply them to exciting biological problems, such as understanding signalling heterogeneity during directed cell differentiation and cancer metastasis. My laboratory is also actively working on understanding how ribosome modifications contribute to regulating protein synthesis (Slavov et al., 2015). I am very excited by all of these projects, especially by thinking of new ways for understanding single-cell proteomics data and new principles behind ribosome-mediated translational regulation.

What’s the biggest challenge your research field faces at the moment?

The biggest challenge is coming up with creative conceptual ideas. This is well illustrated with the development of Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS). SCoPE-MS could have been developed seven years ago if a PI had the idea for it; in fact, we developed SCoPE-MS using only technology that was already present in 2010, and awaited the idea that would enable single-cell proteomics by mass-spectrometry. Now that the idea had been demonstrated, the major mass-spectrometry labs around the world are actively building upon it, using the latest technologies. What was rate limiting was the idea – not the technology.

 

I think that the promising ideas that can enable both new technologies and conceptual breakthroughs outnumber the people who think creatively enough to realize them. In my research area, this is due in part because relatively few biologists understand mass-spectrometry deeply enough to apply it in creative ways to exciting biological problems. More broadly, the development of new ideas is hampered by an excessive emphasis on data generation. The community and the granting agencies reward tangible results, which are mostly easily and speedily produced by applying new cutting-edge technologies to generate large datasets rather than by developing and demonstrating new concepts. I think the progress of biomedical research will be much accelerated if we find a way to reward more conceptual advances and ideas and deemphasize mere data generation.

Name one big development that you would like to see in your field the next 18 months.

I would like to see more emphasis on understanding data rather than merely generating them.

What are you most proud of in your career?

The work I am most proud of is not my best-known work. As a graduate student, I was enthralled by a mysterious phenomenon of emergent cell synchrony that indicated partial coupling between metabolism and cell division. I started working on this project accepting the suggested hypotheses in the field, e.g., that DNA replication has to be sequestered to a reductive metabolic phase, and designing experiments that seemed logical. The experiments worked very differently from expected, and I constantly had to readjust both my conceptual framework and experimental approach. Finally, we discovered that DNA replication is not incompatible with respiration and that hundreds of mRNAs annotated to cell division are expressed periodically even when cells do not divide (Slavov and Botstein, 2011Slavov et al., 2011). I am proud of these results because they required willingness to confront and radically reshape preconceptions based on experiments that allowed for very clean conclusions. Furthermore, I felt (and still feel) that we were among the few people who could have done this research, and thus we could make a non-redundant contribution.

Which scientists, living, dead, or fictional, would you invite to dinner, and why?

I would invite Hans Bethe, Richard Feynman, and Julian Schwinger. These scientists were brilliant but their brilliance appears quite different, and I would love to see the dynamics of their interactions. Also, I would love to have dinner with Michael S. Brown and Joseph L. Goldstein to see the interactions in such a great team.

What advice do you wish someone had given you at the start of your career?

Young scientists can best advance their career by working on very important and promising problems for which they have strong aptitude and which can be appreciated contemporaneously by the mainstream community. I have always had the tendency to ignore the last part, the contemporaneous appreciation, and be partial to ideas that I think are visionary and by implication hard to be understood and appreciated contemporaneously by everybody. Yet, building a career requires that at least some of the work of a young scientist can be easily understood and appreciated contemporaneously by the mainstream community.

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