The Crystallographic Community

Interview with James Fraser, joint winner of the 2020 W. H. and W. L. Bragg Prize

James, we would first like to congratulate you on winning this prestigious award. 

Could you tell us a little about your childhood and early education.

I was born in Toronto (literally across the street from where Jean-Philippe works now!) and attended fantastic public schools my entire life. My mother was a teacher and my father was a civil servant in the Ontario provincial government. Growing up I was obsessed with sports and especially the statistics in baseball and hockey.

What or who inspired you to pursue a career in science, and what attracted you to your field?

By the middle of high school, I wasn't really interested in science as something to study beyond high school. Although I had always done well in math and science, I never really was that excited about it. That all changed when I got to do some hands-on molecular biology thanks to a great teacher, Angela Vavitsas, who was able to get us access to some simple stuff like restriction enzymes and gel electrophoresis in our high-school biology lab. I got hooked by both the conceptual and mechanical (pipetting, etc.) aspects of it and haven't looked back.

Of which of your professional achievements do you feel most proud?

Although I'm proud of everything we have done in the lab, recently I'm most proud of the work a postdoc, Mike Thompson, has done getting time-resolved temperature jump experiments to work. The idea is what if we could nearly instantaneously heat the solvent that surrounds the protein and watch as the protein equilibrates to the new effective temperature. Mike got this working by SAXS (Thompson et al., Nature Chemistry, 2019) and will publish some initial results by diffraction later this year. The diffraction work is awesome because it is the rare time you get to fire not one, but two lasers at something!

What would fascinate the Braggs about your work?

I think they would be interested in the theme of finding data in the imperfections of crystallography. I think the amazing thing about biomolecular crystallography is how even with great crystals, we still do a poor job of modeling the underlying data - what my friend James Holton calls "the R-factor gap". I've been fascinated by the problems of weak density in electron density maps and weak non-Bragg scatter on diffraction images for a long time. There is a lot of exciting work left to be done.

Currently, cryo-EM and X-ray crystallography are complementary approaches to structural biology and drug discovery. Do you see this changing in the future?

Yes, undoubtedly it will change. Right now the throughput of crystallography, especially for drug discovery, is unparalleled. But, there are paths for EM to catch up even in that respect eventually. The exciting things for crystallography are to do the things that EM can't do. Ultra-high resolution studies on small proteins. Fast dynamics. I see more and more labs (including my own) becoming agnostic to the method and focusing more on the common modeling challenges.

Since you were nominated for this prize, the world has been devastated by the coronavirus pandemic. Have you channelled any of your work into coronavirus research/education?

Yes, I've become part of a large effort, spearheaded by Nevan Krogan, here at UCSF to characterize the host interactome. Nevan's group identified hundreds of human proteins that are "hijacked" by SARS-CoV-2 proteins. There are two next phases that interact, identifying small molecules that can break those interactions and structurally characterizing the interfaces. Members of my group are working on both aspects as part of the UCSF QBI Coronavirus Research Consortium. I'm also optimistic that the sharing of data (for example the inspiring Mpro work out of Diamond Light Source) and increased use of preprints will help change the culture of science to prioritize more open and equitable practices.

You run your own lab. In a nutshell, what is your philosophy behind maintaining a happy and productive lab and mentoring its members?

I think I've improved a lot as a mentor by trying to keep my focus on where people in the lab are going next in their career. When we align our scientific goals with their career goals beyond my lab, we can do the best work together. Both the science and the career ambitions naturally change - and being open and communicative with each other about what we desire and what is realistic is the hard work of mentoring.

[Fraser Lab]


What are you seeking to accomplish in your career?

I don't know that this question drives me as much as it used to! Right now I'm interested in continuing to do the science that I find interesting and making sure that the folks who pass through my lab have a great time while they are there and are set on a great track. I've really enjoyed seeing how ideas that started in my lab have blossomed as trainees have moved on to their own positions in academia and industry. A major goal of mine is to reshape the way we communicate our science - I'd like to see us move to completely open lab notebooks and away from "saving" stuff for journal articles.

What other interests do you pursue?

Parenting! I have two young sons, who I spend most of my non-work hours chasing around. The shelter-in-place period of the recent pandemic has put a major emphasis on that!

Thank you very much for your time and congratulations once again