(Still) Surfing the Proteomics Wave
Sitting Down With… John Yates III, Ernest W. Hahn Professor, Departments of Molecular Medicine and Neurobiology, the Scripps Research Institute, California, USA.
On your Twitter profile, you describe mass spectrometry as “the coolest method on the planet” – why is it so compelling?
The simple answer: because you can do almost anything with it – help develop new pharmaceutical drugs, uncover cheating in sports, carry out life-saving newborn screening, and the list goes on...
When did you see your first mass spectrometer?
In 1981 – it was a Hewlett Packard GC-MS and it was love at first sight. Though I must admit, I was mainly fascinated by the fact that there was a computer attached to it. PCs were not commonplace back then, and I thought it was so cool that it had a computer, with libraries where you could match up compounds.
Where do you get your inspiration?
I like going to meetings outside my own field, where I have a chance to meet new people and hear new ideas. It’s thought-provoking to hear about challenges in other fields, and think about how mass spectrometry might fit in. The only problem is that I’m constantly spotting new potential projects, and I have to be careful not to get distracted from the work I already have underway.
How important is it to communicate your science?
In my view, publication is still incredibly important, and it’s something I emphasize to my lab members all the time – your science essentially does not exist until you publish it. I believe innovation moves at the speed of publishing.
How can we speed up publication?
I’m Editor of the Journal of Proteome Research (JPL) and we have made speed a real priority. Right now, the biggest bottleneck in the review process is finding reviewers and getting them to respond in a timely manner. So I’m very interested in new ways to do peer review, including the use of artificial intelligence to pre-review papers. Publishers already use software to spot plagiarism; one day I hope we will be able to automate other aspects of copy-editing, leaving the peer reviewers free to focus on core scientific issues of significance, data analysis, and so on.
What else do you hope to achieve as Editor?
Part of the mission of JPL is to encourage researchers to include biological validation of results coming out of proteomics experiments. We don’t want authors to be satisfied with publishing a list of protein differences between A and B; we want them to show that the change is contributing to the phenotype.
Looking to the future – where do you see proteomics going?
Single-cell analysis is certainly a hot topic right now. The recently launched Human Cell Atlas project (www.humancellatlas.org) aims to uncover the transcriptome of over 10 billion cells throughout the body using RNA-Seq. It would be great to do the same at the protein level. There are a number of young researchers in the mass spectrometry proteomics field who are looking at strategies for single-cell analysis, with some very exciting results so far. It’s also possible that new technologies will come along that don’t rely on mass spectrometry at all – there have been some interesting experiments looking at applying nanopore technology used for DNA sequencing to intact protein analysis.
Proteomics hasn’t been as well funded as genomics – is that changing?
Proteomics tools are used for almost all protein-related research so grant money is being spent on them, but we haven’t seen funding for dedicated proteomics centers as we have with genomics, and I’m not sure if that is likely to change anytime soon, as proteomic driven studies are inherently more complicated than genomics.
Are you concerned about the future of science funding in the USA?
There was a lot of concern among scientists after the current administration proposed large cuts to the NIH for 2017/18. Thankfully, the US Congress pushed back and actually raised the NIH budget for the first time in six years. When budgets are tight, the people who suffer most are young researchers – they are next generation of scientists that we should be nurturing, not chasing out of the field.
You were recognized for your leadership in the 2017 Power List – what makes a good leader?
First, I make sure my team members have everything they need in terms of money, support and expertise. And then I give them the freedom to be creative and explore. A case in point was when Michael MacCoss and Christine Wu came to me with the idea of introducing stable isotope-labeled amino acids into mice that could be used as internal standards for quantitative proteomics in animal models of disease. It was an expensive experiment, and a gamble – we had no idea if it would work, or if the animals would even eat the labeled feed. But it did work, and proved a valuable tool.
Who are your scientific heroes?
My PhD supervisor Donald Hunt was (and still is) a very imaginative and creative scientist, and my postdoc mentor Leroy Hood gave me a vision of how technology can drive science – both were important in shaping my view of the scientific world and my place in it.
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