Chris Wooton

Chris Wooton, Ph.D.

Interviewed by Mervyn Lewis, Associate Editor

Originally published May 2022

What was your impression of mass spectrometry when you were first introduced to it?

The first time we did real MS interpretation was the first time I met Pete (Prof. Peter B. O’Connor) at the start of my second year of undergrad chemistry. We’d never seen ESI-MS spectra and barely knew what a peptide was. We were given a surprise test; here is an FT-ICR MS FID raw signal, learn how to code your own data interpretation program in MATLAB, code the Fourier transform, process the data to frequency space, then calibrate to a mass spectrum, analyse the fragmented peptide, then de novo sequence it, and hand in the sequence correctly by the end of the afternoon, or fail.

It was an interesting introduction, a bit of a trial by fire. After we cobbled together something to do the FFT and present the data, we calculated every amino acid mass into a spreadsheet, then every difference of every amino acid in m/z, and went hunting through the spectra for all these mass differences and figure out some sequence which half made sense. By 5pm we had something, it was hard work but paid off – and MS hasn’t changed much from this conclusion for me, it is always hard work, but we can attack any problem and solve it with enough effort, and that’s a nice position to be in. Pete always sees what people should be able to do if pushed a little, and everyone achieved in the tasks. This is exactly like mass spec; it can seem complicated or difficult, but once you push forward and start getting answers you’ll see so much more and get so much more than any other approach; its always worth it and I wouldn’t want to do anything else.

What persuaded you that mass spectrometry could be a good career option for you? Were you attracted by an application of mass spectrometry or excited by the prospect of developing it as an instrumental technique?

I was a masters student looking at PhD positions, I spoke to Pete and he gave me a tour of his lab and what they were working on with FT-ICR MS. After just 20 minutes of chatting I was amazed at what MS, and especially MS/MS could do, and there was no doubt; that’s what I wanted to pursue for the rest of my career.

I had been in a synthesis lab for months trying to create and characterise new species and realizing that proving you have made something special was at least half of the work. But you really needed purified, separated compounds for most techniques. As soon as I learned that you could scan a whole mass range and then isolate individual species for fragmentation and charactersiation; that was a game changer, and I couldn’t believe this wasn’t applied to all areas of chemistry where I knew people were struggling with complex samples that needed analysis but couldn’t achieve this with other approaches.

I dove into applications and really enjoyed all of it. After a while I found that to get better analysis for our most challenging samples and ambitions; we needed new techniques and instrumentation to accomplish this, so then moved into instrumentation to further pursue these ambitions and possibilities of analysing ever more difficult species and samples. So definitely a bit of both – I really like creating and developing methods and instrumentation to enable the applications we do that make the technique so unique and impactful.

How did you go about finding your first opportunity in mass spectrometry?

I read through over 400 PhD proposals and position descriptions when I finished my Masters degree. A lot of the most interesting ones were already filled, but the adverts were left up to snare candidates and waste time/hope. I used to read dozens of papers from each academic before even asking for an interview, this ended up not being the best use of time/motivation.

I walked into an interview with Prof. Peter Sadler at Warwick expecting to talk about a PhD in synthetic chemistry, he said it was a joint project with Pete and told me to just pop in to chat on the way out, so I did, he gave me a “surprise interview”… it went well and I got to see what they could do with FT-ICR MS and was hooked. Eventually I ended up being 100% on the MS side of the project in Pete’s group and couldn’t have asked for a better start in MS.

I stayed at Warwick for my PhD and a number of Post-Doc grants. But conferences were the best places to meet people, and I was always heavily encouraged to go to any and all conferences I could attend. At BMSS 2019 in Manchester I was approached by the FTMS experts from Bruker, they knew of our work and the research group and were looking for new people. I went to tour the facility in Bremen 2 months later, and 2 months after that I was hired as head of MRMS (aka FT-ICR MS) instrumentation R&D.

Going to conferences is the most important and impactful experience in  research – the opportunities are numerous and available to anyone who loves their subject. The stipend/travel grant schemes run by the BMSS, ASMS, etc were key to this for me and really facilitated creating good opportunities and a network of people to collaborate and communicate with – I couldn’t recommend or appreciate them enough.

In what application fields do you see new opportunities in mass spectrometry?

Truly complex mixtures and MS/MS. Metabolomics, environmental samples, petroleomics, and any complex biological samples. From a conference recently I was greeted with the phrase “you cannot identify any compound by MS without MS/MS”. And this rings very true. Once you have identified a compound comprehensively through MS and MS/MS measurements, you can easily observe the species again at the same m/z and say retention time to be happy you have observed a certain species. But without the MS/MS you could not truly identify a compound. There is a lot of scope for analysis of truly complex samples, which by requirement of available techniques and patience often require purely MS analysis, or LCMS with only a certain proportion of species being studied by MS/MS. But this leaves too many questions that quadrupole-based isolation cannot accurately answer due to contaminated MS/MS spectra. New opportunities in UHR-MS/MS (as in – resolution of the MS/MS, not the mass analyser) are sorely needed to get MS/MS spectra of every species, every time, and without ambiguity over their original parent ion. Developments in IMS are definitely a driving force of similar dreams, by separating species based on a different metric and enabling the isolation of target species for MS/MS this really extends the complexity ceiling for analysis of complex samples. Combinations of IMS and UHR-MS/MS are needed for the challenging samples of the future. We can see many tens of thousands of species in some samples – it would be great to see tens of thousands of MS/MS spectra to match every one of them and allow identification.

What is your opinion about the impact that automation and informatics will have on mass spectrometry?

Automation and informatics are key to realizing the true power of MS and MS/MS analysis. They enable scaling up to true impact of the techniques we develop. But should be approached and validated with caution, through critical analysis of every step and every assumption made. This can really open new routes to analysis and generate vast quantities of data needed for large scale conclusions, as long as it is done carefully and accurately.

I believe there is a healthy balance point between embracing new technology and approaches, but also putting the effort and work into making sure they are fit for every purpose and conclusion we plan for them. Only careful and considered approaches survive the initial hype of an idea and make it to true impact on the field/society, and there’s a good reason for that.

These techniques have and will continue to change the balance from the mass spectrometrist knowing if the result is good, to waiting for software to tell them/decide if it is good or not. This can be very useful, or very dangerous depending on how it is handled and implemented.

Nothing echo’s this more than automated analysis of data and the resulting conclusions. It is very easy to create situations which will show you the answer you want, it does not mean this is in anyway related to the true answer, the devil really does hide in the detail and it is the responsibility of the mass spectrometrist to ensure the fidelity and accuracy of their analysis and their data acquisition.

Those with close relationships to definitive and unnegotiable relationships to their data (e.g. medical MS work/diagnosis) tend to produce the most critical view of their data and thus the most robust interpretations and practices, these approaches are refreshing to see and avoid the misconception that the commonly found answer is somehow the right one, whereas unfortunately the opposite is normally true for many challenging analytes.

Automated identification of biological systems or diagnosis using MS-based approaches (e.g. cancer/ bacteria) are already known and will continue to develop and surpass previous judgement based approaches in both speed and accuracy once enough basis work is done.

It will be exciting to see the new tests or diagnoses which previously required interpretation/judgement which will now be answered directly with accurate MS based analysis.

Could you describe your views on career prospects in mass spectrometry for young people?

Mass spectrometry is an ever-growing field with a distinct feeling of manifest destiny to it. Whatever we have in the world; we can get an MS analysis of it, one way or the other. And this is a great field to grow a career in. Find something you are passionate about and push forward. Hard. Then you can make a real impact anywhere with MS behind you.

The mass spectrometry field provides opportunities in so many areas for anyone who is willing to work for it, which is very liberating and it's great to be in a field which reveres data and hard conclusions above all else.

It’s a great multi-disciplinary field which benefits from the diversity of the researchers who exist within it. Be that the physicists improving the fundamental instrument performance, the chemists improving methods and understanding, or the biologists creating and preparing the weird and wonderful samples which challenge our instruments and researchers every day.

There are so many areas mass spectrometry has made advances into, and many more on the horizon – any research group or department which wants to study what exists in the world can benefit from one of the many flavors of MS, they just need to be told what it can do.

We are a group of problem solvers and curious minds who like to figure things out – if that sounds like you then you might want to give mass spectrometry a good look as it’s a great place to be and a great time to join.

Acknowledgement:

Dr. Christopher A. Wootton is currently Manager of MRMS instrumentation R&D at Bruker Daltonics GmbH & Co. KG, Bremen, Germany where he has the great fortune of developing the highest performance and most flexible instruments in the world – FT-ICR MS. He continues to work closely with his Professor; Peter B. O’Connor of the University of Warwick who not only gave him the opportunity to start in mass spec, but has worked with for many years and made him the mass spectrometrist he is today.