When people think of what it means to be alive, they often focus on genomes—which encode biological information and enable its transmission and evolution. By themselves, however, genomes aren’t enough to live on: where the rubber meets the road, it’s the proteins encoded in genomes and the metabolites that those proteins operate on, that transform genomic information into biological action. New generations of chromatography and mass-spectrometry technologies enable researchers to ask detailed questions about these biomolecules on a truly grand and simultaneously nuanced scale. In a continuation of a series focused on highlighting the Shared Resources at Fred Hutch, I sat down with Dr. Phil Gafken, Director of the Proteomics and Metabolomics Shared Resource, to talk about his path to science, how the resource enables world-class cancer research at Fred Hutch, and his advice for those starting out in science.
Could you introduce yourself, and your path to science?
I didn’t have the most direct path to science, but I guess when I was in school, science and math were always some of the most interesting topics to me. One early memory that I can recall was when I was around 8 or 9 years old, my brother and I got a ‘geology/chemistry kit’ for Christmas. This was the 70’s (so the safety standards weren’t as rigorous as they are today) and these kits had methanol, alcohol burners, all sorts of crazy stuff. Long story short, I got into combustion chemistry very early on! That kicked off sort of a long-term interest in chemistry. I started undergraduate intending to go into medicine, but by about three-quarters of the way through college, I just counted up all of the chemistry courses I had taken, and I thought ‘man, maybe I should just make chemistry my major,’ and I did. I ended up getting an internship working for the federal government doing trace metals analysis, which turned into a permanent job once I graduated. That job was fun but eventually got pretty monotonous—I decided I wanted to steer more in the life science direction, so I went to graduate school at Oregon State University, where I discovered chromatography during one of my rotations. I also rotated in a mass spectrometry lab, and I ultimately realized that the combination of the two techniques really appealed to me, so that’s kind of where I am now. When I finished graduate school, the proteomics field was brand new—even the term ‘proteomics’ was new—and I was incredibly lucky that the field was absolutely white-hot right when I was looking for a job. I sent out three resumes and got three responses. Incidentally, the first response was from the Hutch, so I came here for an interview—that was 24 years ago, and I’ve been here ever since.
What drew you to Fred Hutch over other places?
I distinctly remember being interviewed by Dr. Jonathan Cooper [who still runs a lab in the Basic Sciences Division studying cancer cell migration and morphology], who told me ‘You know, just keep in mind that—if you take this job—you’re gonna be the only person around here who knows anything about mass spectrometry and proteomics. We’re happy to help but we can’t provide a whole lot of it, so you should be prepared to be on a bit of an island in that way.’ Now someone could look at that and think oh my goodness, I’m on an island by myself! or they can think Hot dog, I’m on an island by myself! and I fell into the latter perspective there.
That’s an interesting sentiment, that the lack of a mass spectrometry/proteomics community at the time that you joined the Hutch could be seen as a bad thing or a great thing, depending on your perspective.
There’s an old joke about this—one shoe salesman goes to an island, notices that nobody on the island wears shoes, and goes back to his boss and says, “Forget it, this is a lost cause. Nobody on this island wears shoes!” A second shoe salesman goes to the same island, sees the same things, and goes back to his boss and says, “Nobody on this island wears shoes! Give me all the shoes that you got, let’s start selling.” So sometimes it does seem like perspective can dictate a lot.
What was your role when you started at the Hutch, and how does it relate to your current role?
When I started here, there was a single mass spectrometer, upstairs next to Dr. Steve Hahn’s lab [who also still runs a lab in the Basic Sciences Division]. Every now and then it would get used for a few experiments, but inevitably the person who had learned how to use it would move on to a different career stage, so they had to constantly keep training and re-training people on the instrument. I came on as a staff scientist partly to address this issue and help maintain the instrument in a more permanent manner. Eventually, as mass spectrometry became more in-demand, we expanded on this and turned it into a larger resource for the Center, which sort of propelled me to my current position as director of the shared resource. Nowadays, we have four staff members—three are chemists/biochemists and one is a data analyst.
How would you describe the value of the Proteomics/Metabolomics Shared Resource to someone who might not be super familiar with it?
So, we collaborate with Hutch scientists to perform a range of proteomics and metabolomics services—anything from simple identification of an unknown protein in a gel band, all the way to proteome or metabolome-scale identification and quantification of molecules in a variety of biological samples. Unlike a few of the other shared resources, which train and support researchers to use their technology, my staff are the only ones that actually operate our instruments [important side note: mass spectrometers are very sensitive (and expensive) machines]. We do, however, strive to train people as much as we can within those constraints and educate them on the technology so that they’re set up to do the best science that they can—this includes one-on-one training from our staff, and I also teach a five-day course on the principles of proteomics every year.
Just because I’m curious—what’s your most expensive instrument?
The most expensive instrument that we have is our latest-edition mass spectrometer—called an Orbitrap Ascend—which cost 1.2 million dollars. What I like to tell people, though, is that these instruments are a lot like cell phones: as soon as you walk out of the store with the new, flashy cell phone model, they come out with an even newer model which is better in every way! So, a distinct part of our job is playing this cell phone game on a larger scale: closely following new developments in these tools, and evaluating new technologies as they are released to determine whether the added capabilities are really worth investing in.
What are your favorite and/or least favorite aspects of your job?
There are so many good parts about this job. I certainly like the institution—when people ask me why I’ve stayed at the Hutch for this long, I often mention the degree of autonomy that I am afforded here. When I started to think about that a little more, though, I realized that this autonomy really stems from a fundamental trust and confidence that the Hutch has put in me and my staff—confidence in our judgement and abilities to do our work. I think this relationship that we have to the Center is pretty unique and has worked out very well over the years, and it’s a major reason why I love working here. It’s also fun to be exposed to such a wide variety of science—I might say that I’m an expert in proteomics, but I’m definitely not an expert in anything else! Even though I’m not the best biologist, though, the opportunity to experience and participate in really diverse and cutting-edge work has been a lot of fun. As far as less-fun aspects go, some of the administrative tasks—keeping up with and securing funds for new instruments, making sure the instruments are maintained and repaired as needed, hiring new staff—are necessary but sometimes stressful parts of the job.
What’s a typical workday look like for you?
I feel lucky that my staff and I are involved in nearly every aspect of the research enterprise—everything from working with researchers to conceive and propose projects, to planning proteomics/metabolomics experiments, to collecting and analyzing the data, and figuring out how to best communicate the results. So, I’m involved in a lot of that; I’d say that roughly half of my time is spent working with experiments in some capacity. Over the last year or so, I’ve had less time to work with the instruments, but there was a time not too long ago when I still spent a significant chunk of time in the lab.
I imagine that you’ve witnessed a lot of changes at the Hutch and in the mass spectrometry field since starting the role—could you comment on that?
Certainly—I mean one surface level detail is how digital our communication has become. I remember a time when there were only a few main users of the resource, and I used to just walk down the hall or up a floor to discuss results or chat about ideas. Nowadays, I spend a lot more time sending and answering emails! On the more scientific side, there have definitely been trends in the usership; when I started, for example, most of the users were labs in the Basic Sciences Division, and we were measuring things like histone modifications in model organisms. Starting around the time when Lee Hartwell was president and pioneered initiatives for early detection of different cancers, we started doing a lot more serum proteomics from patient samples for the folks over in the Public Health Science Division. I’d say more recently, we’re much more involved in translational and clinical research in addition to continued users from more basic-research focused labs. Of course, the technology has improved exponentially from the time that I started (when the human genome wasn’t even published yet!). I’d say that even though many species’ genomes are sequenced now, faithfully annotating and understanding the proteomes of all these species—which tend to be more complex than their genomes—is very much still a work in progress, but with the help of new technological advancements we’re making good progress towards these goals.
Do you have any particularly memorable experiments?
One time, a group from Brazil sent us protein extracts from fluorescent mushrooms—I didn’t even know those existed! So that was pretty memorable and fun.
How would an interested researcher get in touch with you guys to start a collaboration, what advice would you give them, and how should they best acknowledge the shared resource’s contributions?
I would definitely encourage anyone interested in proteomics or metabolomics to shoot us an email (proteomics@fredhutch.org or metabolomics@fredhutch.org). As for advice, I would encourage interested researchers to contact us as early in the experimental process as they can—sometimes interested parties come to us with already-collected samples, and we miss opportunities to help design better experiments to maximize the robustness and usefulness of the resulting data. As far as acknowledgement goes, I wish there was some sort of litmus test to determine when a certain amount of contribution warrants authorship—I guess if I had to draw a line, if our staff provide a figure for a publication, or has been meaningfully involved with the development of a project, I would consider that enough of a contribution to warrant authorship. Ultimately, though, the vast majority of the work we do is fairly straightforward assistance with mass spectrometry methods, which we would expect to be acknowledged for. I should point out that it is important for any Shared Resource used in a manuscript to be listed in the acknowledgements. This provides a means to measure the contributions of the Shared Resources to the science at Fred Hutch and results in metrics that can be reported either to senior leadership or to the NCI Cancer Consortium grant to reflect our value. I invite authors of manuscripts that utilized any shared resources to view our webpage on suggested language for acknowledging Shared Resources.
If you could give one piece of wisdom or advice to a trainee or someone starting out in science, what would that be?
I think I have two pieces of advice. The first is to do something fun—it’s just so much easier to get out of bed in the morning and do so consistently, and life is too short to not have fun doing what you’re doing. The second piece of advice—which might be a bit contradictory—is that you don’t have to take advice that is given to you! I remember, for example, that when I got my first job offer (from the Hutch), lots of people told me that I should never take the first job offer. I decided not to take this advice, and over 24 years, I’ve never regretted that decision.
For more information about the Proteomics and Metabolomics Shared Resource and to get in touch, check out their website.