On a Collision Course
Sitting Down With… Vicki Wysocki, Professor, Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA
James Strachan | | Interview
Tell us about your main line of research, surface-induced dissociation…
When I joined Graham Cooks’ research group at Purdue, the group was trying to intentionally collide ions into surfaces as an additional activation method for tandem mass spectrometry. They successfully implemented the surface-induced dissociation (SID) method, but instruments of the time could only ionize and transmit small molecules (up to about 10,000 Da if ionized via fast atom bombardment). As it became possible to ionize and transmit much larger ions into mass spectrometers, my lab incorporated the surface collisions of these species into a variety of instrument types. Surface collisions, by virtue of increasing the energy in a large step, fragment large non-covalent protein complexes into structurally meaningful subcomplexes.
Though collision-induced dissociation (CID) can provide structural information, its low energy, multistep activation can also significantly restructure protein complexes. If researchers are careful and know what they are doing, they can use CID in a structurally meaningful way for non-covalent complexes, but they may also inadvertently produce misleading data. Currently, we use native mass spectrometry and SID as complementary techniques with other structural biology tools such as cryo-electron microscopy.
Tell us about your mobile proton model.
Peptide fragmentation is important because peptides are the building blocks of proteomics. The mobile proton model explains qualitatively why and how different peptides fragment in different ways. (Some fragment extensively, with peaks from the population of fragments indicating cleavage between every pair of amino acids; others fragment quite selectively, with one main cleavage site dominating the fragmentation spectrum.)
By the late 1980s and early 1990s, several groups had started to see interesting fragmentation patterns in peptides. I wanted to understand some of these features better, so my group used SID to characterize the fragmentation patterns of chosen model peptide systems. We then expanded that to what I think of as early “big data” experiments with data provided by Dick Smith and colleagues at the Pacific Northwest National Laboratory.
When I first sent some of our early “mobile proton” results and conclusions to my former colleague and friend, Hilkka Kenttamaa, at Purdue, she mentioned that she had seen some recent (at the time) work by Simon Gaskell with similar conclusions. I approached Simon and we ended up publishing some work together. That’s why, when I was asked about being nominated for the ASMS Distinguished Contribution to Mass Spectrometry Award, I requested that Simon and I be nominated together for a joint award. It was clear, as often happens in science, that our work had many parallels.
In fact, when Simon and I met to discuss our joint talk for the award presentation, I learned that Simon, with his British roots, had considered calling the model the “roving proton” model. A colleague at a conference once said something like, “But Vicki, it’s so frustrating – you can change just one methyl group on a peptide and its whole fragmentation pattern might change.” That’s what I find so fascinating; relatively minor structural alterations can cause significant fragmentation pattern changes. By looking at a few models and then a few thousand spectra, we got a pretty good handle on big-picture predictions of peptide fragmentation behavior. The finer details have since been worked out by many talented investigators. Many groups, including mine, have collected infrared multiphoton dissociation spectra of fragment ions in the gas phase to better characterize the product ion structures. Experiments and computations by several groups (Armentrout, Paisz, Maitre, Oomens, and others) have characterized features such as mechanisms of proton transfer and ring closures.
Why do you so frequently collaborate with experts outside your group and across different cultures?
One of the wonderful things about science is that the main things that you need to bring to the table are your willingness and ability to think and your tenacity. Bringing together people of different backgrounds leads to the greatest progress. Group members learn by working with others from different personal and scientific backgrounds. A recruiter from industry once told me, when I asked, that what they look for in new hires is people who can work well as part of a team. By working with a diverse group internally and collaborating with others outside the group, including making regular presentations to collaborators, group members become mature scientists who work well in their future environments.
What gets you out of bed in the morning?
The main thing that drives me is scientific curiosity – the need to discover something – but also the drive to share findings with others and to make it possible for them to use our discoveries for their own purposes. I also love watching students learn and mature as they carry out their research. It is very rewarding to see them branch out into their own careers in which they innovate and improve daily life for others. Each person may think, at times, that their contribution is not enough, but all of us are needed to improve the world.
Although I don’t perform my own experiments anymore, I enjoy tremendously attending our weekly group and subgroup meetings to see what new discoveries have been made. I appreciate cooperativity in research and highly value group members’ making suggestions to each other on how to improve their experiments. Though I am not able to get into the lab during the academic year, I do try to take a trip each year that allows me to sit at an instrument and guide experiments. In recent years, these trips have primarily been to CLIO in France and FELIX in The Netherlands, along with short pre-COVID-19 stays of one to two months in Tom Rizzo’s lab at EPFL in Lausanne and in Michal Sharon’s lab at the Weizmann Institute.
What are your main goals for your group?
A couple of exciting things that we are currently working on are the coupling of SID with charge detection mass spectrometry and with electron capture charge reduction or electron capture dissociation. We also have a plan to try some “matrix landing” experiments in Josh Coon’s lab at the University of Wisconsin. It will be a real treat to see electron microscopy images for ions that have been electrosprayed, fragmented by SID, and landed on a surface.
Looking back at your career, what has been your biggest reward?
I would say that my biggest reward has been seeing my PhD students move on to careers in universities, government labs, chemical companies, clinical labs, biopharma, and instrument companies. Most of them have stayed in the mass spectrometry field and make innovations regularly. They are enthusiastic about what they do, and I enjoy seeing their progress. I’ve also enjoyed taking a particular scientific path (collisions of ions with surfaces to provide structurally informative fragments) and building it over what has become decades.
Modern mass spectrometry experiments are amazing and build on the work of many people from academia and industry. So many different innovations in ionization, ion transmission, ion analysis, and detection all come together into experiments that wouldn’t have seemed possible when I entered the MS field.
Which characteristics have helped you most?
Persistence is a characteristic in which I think I excel. When I find a problem interesting, I like to continue tackling it until we solve it or at least make good progress. Insight grows from persistence; the more time you spend on a problem, looking at it from different angles, the more likely you are to gain insight into it. Often, and especially if you think you are not making progress, it’s good to take a break from the problem and come back to it with fresh thoughts.
Maybe I should also comment on originality. I don't always think of myself as original or creative, but I do enjoy taking a body of data and trying to generate new meaning from it. In that sense, I think I can be original by finding the hidden stories in datasets or planning experiments that have not been done previously.
How have you found serving as ASMS President?
ASMS is a wonderful society. The members are a loyal group and we always have large numbers of volunteers for any job. During, before, and after my term, the society has worked on increasing diversity, equity, and inclusion (e.g., in selecting session chairs and speakers, in committee selections, in publishing, and so on) – making sure multiple voices are heard throughout the society’s functions. There is still a long way to go though so I hope all members continue to work hard to make the society more inclusive.
The presidential term is not just the time spent as President. It’s a six-year term in which you first serve as the Vice-President for Programs, putting the annual conference program together for two years; next, you serve as President for two years; and, finally, as Past-President for two years. It is an honor to serve in the position and to witness the large number of volunteers who give their time to make the society successful, working with a fantastic Scientific Association Management team.
I got to know many society members throughout my term at ASMS and also worked on our current co-publishing agreement with the American Chemical Society. I now benefit from that arrangement as the newly selected Editor-in-Chief (EIC) of the society journal. I believe that my time as Vice-President, President, and Past-President of the society has provided me with a foundation that will help me in my role as Editor-in-Chief. After serving ASMS, I have also served as a councilor, and now an officer, of the Protein Society. That has provided an opportunity for me to take advantage of my ASMS experience to contribute to another scientific society.