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Cathy Drennan is a Section Head in Chemical Biology, based at Massachusetts Institute of Technology.

F1000: What are you working on now?

My lab uses X-ray crystallography and other structural techniques to investigate complex metalloenzyme funtions. Currently, one of the things we’re most interested in is this pathway, that involves multiple metalloproteins, that allows certain microbes–acetogens–to live on carbon dioxide as their carbon source, which they convert into acetyl CoA. This involves, from the bioenergetic perspective, formation of carbon-metal bonds. That’s pretty exciting: you form bonds between cobalt and carbon, and nickel and carbon, and it converts carbon dioxide into fuel for the organism to use. We’re solving structures of all of the enzymes in this pathway, both separately and in complex, to see this “carbon hand-off” from one metalloprotein to the other.

F1000: How did you get interested in this pathway in the first place?

I actually became interested in it first because I was interested in vitamin B12, which I had worked on as an undergraduate at Vassar College with Miriam Rossi who had studied the structure of the free vitamin, with Jenny Glusker who was trained by Dorothy Hodgkin, so there’s this line of crystallographers who all studied the same vitamin! I’m proud to be part of that distinguish lineage of female crystallographers who’ve worked on vitamin B12. In my graduate work I worked with Martha Ludwig and determined the first structure of vitamin B12 bound to protein. B12 is amazing, it can do radical chemistry, and it can also do this methyl transfer chemistry (transferring from folate to vitamin B12), it’s an incredible nucleophile and also a generator of free radicals: I just fell in love with the vitamin B12 chemistry. This particular pathway, there were no structures when I started working on it of anything in this pathway; so I was first attracted to vitamn B12 and then fell in love with the entire pathway.

Coincidentally, the hardest structure to get was the one protein that had the vitamin B12 cofactor; we determined all the other structures first. But we’re getting the whole pathway and eventually we’ll have the whole thing, but I became interested in the thing that turned out to be hardest to do!

F1000: Who has inspired you?

I’ve had some really amazing role models at every step of my pathway, including my parents. My mom was an anthropologist and my father was a medical doctor. My mom had a PhD and they just always encouraged me to figure out what I thought was interesting and to go for it. At Vassar, Miriam Rossi was amazing and I’m still in touch with her–she still gives me advice! Then Martha and Rowena Matthews in graduate school were both amazing advisors for me. Doug Rees at CalTech–I still go to him for advice–he’s been incredibly supportive. At MIT I had senior colleagues who mentored me through the whole tenure process, including [F1000 Section Head] JoAnne Stubbe, Barbara Imperiali and Sylvia Ceyer. So three of the senior women in the department all mentored me in different aspects of my career. I’ve been incredibly fortunate to have so many people advising and looking after me.

F1000: How do view your own mentoring responsibilities, especially towards women?

I have both men and women in the lab and I think that’s great. The thing that’s so amazing is working with young people: the best part of science is the ability to use scientific discovery as a mechanism to train people as scientists, and watching my students really grow and start asking critical questions and designing their own experiments–it’s incredible to watch that process. I love it, it’s the thing that’s the most fun for me, is watching them exploit the scientific process, making that discovery, realizing what it means, or thinking or seeing something in a structure I haven’t even noticed. It’s like “Wow, that’s your discovery.” That’s the most amazing thing.

F1000: What’s the best piece of career advice you’ve received?

There’s one piece of advice that I think sounds really silly but to me it was very meaningful. At Vassar College, there was a female computer science professor about to retire, Dr Asprey, and I took her Fortran class, and she said something like, in your life you’re only going to write twelve error-free programs. And she said, “Don’t waste it on something simple.” I thought that was such a great idea; in life things only work well–fast or without mistakes–so many times. You don’t want to waste it on a simple experiment, you want to save it till when it really counts. It took me a while to graduate with my PhD, and I was like, “Great! I saved the easy experiments till later when it really matters.” I love that concept that instead of being frustrated, you can look at it like “This is a trivial experiment, and now, when I do the hard experiment, it’s going to work perfectly.” I know life isn’t exactly like that, but I just feel like it’s a really good way to look at when things are not working and keep your spirits up and keep going!

F1000: What are your plans and hopes for crystallography as a field?

I think that what’s really exciting in the future is as things like determining structures become easier to do, that more people will have the time and ability to relate what they’re seeing to what’s happening in the cell, and to really think in three dimensions about the data, becoming really good at analysing and thinking about the significance of things. Too many times we don’t really conenct all of the pieces of information. There’s so much information being produced in science all the time and everyone has their little pieces, but to have people trained who are real critical scientists, real thinkers, able to relate pieces of data from one field to the next and think about its significance, who can really think at the molecular level about structure and its meaning–I find that so exciting. I still hear these talks where someone says “Oh yeah, we have a structure and it looks like this” and they move on and don’t even say anything about how important it is or what it meant, or what they learned or didn’t learn. I hope for a future where there’s well-trained people who are able to make sense of data at the molecular level, and connect that from the atom up to the molecule to the cell to the human being.

F1000: What’s the professional achievement that you’re most proud of?

There are many results from my laboratory that are very exciting but at the end of the day the thing that makes me most proud is the students that I’ve trained, watching what they’ve been able to achieve and what kind of scientists they’ve become.

F1000: What’s the most interesting unanswered question in biology?

In terms of structural biology, one thing that’s really missing is snapshots of how proteins are interacting with each other, and other biochemical data to fill in the pieces of what’s driving these changes and how fast they are, coming up with molecular movies of what’s happening in the cell. We’re getting there, but understanding [the dynamics of] protein-protein interactions is still pretty challenging. I’m excited about small-angle X-ray scattering techniques to look at more things in solution. Bringing together a variety of structural techniques to probe these kind of things is a really important area where we’re missing a lot of information.

F1000: Do you have any advice for young people starting out in science?

Have fun!

Some students try to game the system way too much. They’re like, “This area’s hot so I’m going to study this,” and they research what people from different labs have done, how fast can they do it, where are the jobs going to be… I feel like science is trendy and you don’t know what’s going to happen, and if you’re having fun with your science, if you’re always addressing what you think is really interesting, you’re going to be successful.

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Listen to Cathy talking about how she got hooked on B12, her mentors and what biological science is missing…

(Download the MP3 if you don’t have the Quicktime plugin.)