Melody (A.B. ’10) is a postdoctoral research associate at the University of California, San Francisco.

Degree: Biochemistry with a minor in German

Current location: San Francisco and Seattle

Year graduated: 2010

Student Organization Involvement: Michigan Pops Orchestra; Pops Chamber Orchestra; American Chemical Society Student Affiliates; Alpha Chi Sigma; independent research in the Koreeda lab; independent research in the Karbstein lab; being in the library

Other jobs or graduate programs attended since graduation: Ph.D. in biophysics at the Scripps Research Institute (2015)

MC: I’m an electron microscopist, which probably sounds a lot more intimidating than it actually is. Electron microscopy falls under the umbrella of structural biology, which pretty much refers to any technique used to study the structure of proteins or complexes. Electron microscopes are similar to light microscopes in what they do (magnify samples), except instead of using light, they use electrons, which allows for higher resolution images. They are also bigger and a lot more expensive. My work entails trying to understand exactly how certain proteins and protein complexes look. If you understand exactly how a protein looks, you can better understand how it functions, how it interacts with other proteins, and what shape molecules might fit in it, which means you can also possibly design better drugs.

 

KC: So you currently live in Seattle… and San Francisco?

 

MC: My husband’s job is in Seattle; he’s a professor at the University of Washington, teaching biochemistry. We actually met in the same lab in San Diego, so we do very similar work. We recently bought a house in Seattle, but I work in San Francisco. I live in SF during the week, and every other weekend I’ll fly up to Seattle, and on the rest of the weekends he’ll come here. It’s pretty awful. I love Seattle so much – definitely more than San Francisco.

 

KC: How did you get into this field?

 

MC: This may sound cliché, but science is a way of understanding the world a little better. I started doing independent scientific research the summer after my freshman year in college. I realized then that when you do scientific research, even if it’s a tiny piece of the bigger picture, you have the answer before anyone else. You’re the first person in the entire world to understand exactly how these two molecules interact or what this protein looks like. And it’s usually on a really, really small scale, but having that knowledge that no one else has for a brief moment is very cool.

In my role, I produce proteins complexes and prepare them such that they can be imaged in an electron microscope (which involves freezing them into a non-crystalline form of ice at about -350 ˚F). I use the microscope and a special type of camera to collect thousands of images of the same protein complex. Although all of these images are in 2D, through a series of data processing steps, I can come up with a map of how the protein complex looks in 3D. These data processing steps are not always entirely straightforward and change based on what type of proteins you’re looking at, so some of the work I do has been developing new algorithms to optimize this step. At the end I’ve been able to get 3D models that are so highly detailed you can visualize individual water molecules. After I have a model of the complex, there are more interpretation steps and biochemical experiments I do to confirm any new hypotheses about the structure.

 

KC: What has been your career/graduate school timeline since you graduated from U-M until now?

 

MC: I actually changed career paths right before I graduated. I was planning on going to the Michigan College of Pharmacy for a PharmD, however my undergraduate research advisor, Katrin Karbstein, persuaded me otherwise. I remember it vividly: she sat me down in her office and closed the door and I was convinced I had broken some expensive piece of equipment. Instead, she managed to convince me to move with her and the rest of the lab down to Scripps in Florida (where she was starting a new position) so I could finish my project and reconsider graduate school. I've never been one to say "no" to an adventure (or an opportunity to finish a project)! So I moved to Florida, deferred my admission to Pharmacy school, continued my project, and applied to graduate schools.

After interviewing at several schools, I decided the Ph.D. program at the Scripps Research Institute in La Jolla was a perfect fit. It is a relatively small school that is extremely research intensive, with a very strong structural biology program–which was the field in which I was most interested. I was funded by the American Heart Association, made some contributions to electron microscopy imaging processing methods, and collaborated with many amazing people (some of whom are now close friends). I finished my Ph.D. in just under four years.

After defending my thesis, I continued working with my thesis advisor, Bridget Carragher, for about half a year, who had since moved to New York Structural Biology Center in New York City. (Note: it is actually pretty atypical that I ended up moving with two advisors-- moving a lab is a relatively infrequent occurrence in academia and I don't know anyone else who has moved with two labs in less than five years.) During this time, I helped mentor new members in the group, did a lot of self-reflection as to whether or not I wanted to keep pursing a career in academia, wrote fellowship applications, and began applying for post-doctoral research positions.

I was being assertively recruited by Pfizer at the time, but I had set my myself an ultimatum: there was one scientist I wanted to work for (Yifan Cheng at University of California San Francisco) and one project I wanted to pursue, and unless I could achieve that goal, I was going to take an offer in industry.

Two years ago, after a flight out to San Francisco and an interview, I accepted a position at UCSF and have been here, pursuing a career in academia ever since.

 

KC: In your work, what are the larger goals that you’re working towards? Do you work on the pharmacology side, are you researching specific molecules for specific diseases, etc.?

 

MC: This is a bit of a roundabout answer because I’m going to deflect: The Nobel Prize in Chemistry was just awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for their contributions to develop cryo electron microscopy, which is exactly what I do. As a result, the field is growing at a very fast pace. There is a ton of overlap between people working on the same things, so recently scientists haven’t been talking much about the exact proteins they’re working on so that they won’t “tip off” a competing group to rush and publish their structure first. I work as part of a team, so if I speak in too much detail about what I’m working on, it not only affects me, but many of my colleagues as well. I can tell you that I’m working on a small membrane protein that is a promising drug target for chronic obstructive pulmonary disease. (When we get this structure published I’m more than happy to tell the whole story!)

I want to mention that this is something that’s only happened in the past five or so years in the field; people used to speak freely about their work and welcome suggestions from others. Only very recently has it closed up. For my career path, it’s important to publish papers about what you learn. That’s the metric that employers use to determine how successful you are. If another group of scientists publishes the same protein as you first, it’s very difficult to publish a paper about it afterwards. You can think of it as racing to be the first to make a map of a new unchartered island. Once the first map is published with a guide to where all the trails and mountains and lakes are, the second map–although some small details may be different and maybe even more detailed–is not nearly as exciting as the first map. It’s pretty competitive right now.

 

KC: Because your line of work is so competitive, does that make your job stressful at times?

 

MC: Yes, it makes it very stressful. When I started in this lab two years ago, both of the projects that I was working on “got scooped,” as we call it (like in journalism). I had been working on one protein for a few months, and then I heard that another group had published the structure. I started a new project–I actually worked on that second project for about a year–and then one day its structure was published by another group too. This is really tough and can be disappointing; imagine working on something for a year, and then one day you come in and read a paper and you think, “Oh… everything I’ve done for the past year doesn’t matter.”

I don’t want to sound pessimistic about it, because I learned SO much from these projects. For that second project specifically, I was purifying membrane proteins in human cells, one of the most complicated systems for expressing and purifying proteins, and also one of the most difficult types of proteins to purify. So I certainly learned a lot of new things and techniques, but in the end I don’t have any publications to prove that I did any of that work. As for least favorite things about the job, that’s definitely one of them. I knew that project was high risk when I took it on, but I was really interested in it. I was actually studying CFTR, the protein that causes cystic fibrosis, so there was a TON of interest in that protein. Sometimes if you work on less interesting things it’s less stressful.

 

KC: What are your favorite and least favorite aspects of your job?

 

MC: Okay, so I think we thoroughly went through my least favorite aspect, which is the stress and competition. As for my favorite… my PI (principal investigator), both the one I have now and the one I had while getting my Ph.D., were both very chill. They trust their students and post-docs to be motivated, keep up with the literature, and design their own experiments. That’s been nice, in that I don’t really answer to anyone. If I wanted to do anything wildly expensive or crazy, my PI might step in, but on a day-to-day basis I can come in whenever I want and leave whenever I want. I can take days off. As long as I’m getting work done, it’s fine. I love the flexibility. I don’t want to make it sound like we don’t work a lot, because we work a TON, we just do it on our own schedule. I’m allowed to pursue my own ideas, which is nice. That gives me a sense of independence.

 

KC: What did you gain from your LSA degree that has influenced your career path?

 

MC: My LSA degree has been instrumental in guiding my career path. Two of the most influential opportunities I was ever presented at LSA were: 1. The accessibility to do research, and 2. The summer abroad programs.

LSA has an absolute abundance of research opportunities for undergraduates. There are so many different labs doing really cutting-edge and novel research in many different fields. Since I was interested in chemistry and biology, it was inspiring to be able to take a course and then to check some references and realize that groups at Michigan had actually contributed to understanding that specific scientific concept. Furthermore, many of these professors were willing to accept undergraduates into their lab to do independent research. I was extremely fortunate that I was able to train with three different professors while at Michigan who not only served as scientific advisors, but mentors as well. In Ann Arbor, I worked for one year in Masato Koreeda's organic synthesis lab and two years in Katrin Karbstein's biochemistry lab.

Additionally, the Department of Chemistry had a unique exchange fellowship that sent several Michigan students out to China to work in labs and hosted several Chinese students in Ann Arbor labs. I spent one summer at Peking University in Beijing to pursue organic chemistry research in the lab of Jianbo Wang. That international experience opened my eyes to a new perspective of how to approach certain chemistry problems, and research in general.

The following summer I went abroad again, but in a very different context. The Department of Germanic Languages and Literatures offered a fellowship to study at a Goethe German Language Institute for a summer. The goal of these language institutes was to attract people from all over the globe and unite them with a single language. Here, I interacted with people of many different cultures who held a wide range of ideas, opinions, and approaches. This experience helped me to improve my global perspective and communication skills which are key in my daily interactions with collaborators and colleagues.

 

KC: What advice would you give current students hoping to follow in a similar career path?

 

MC: Make sure you really want to do it. Michigan is great in that it has a lot of different labs, and the labs are happy to take on undergraduates. That’s certainly not true at every institution. So get yourself into a lab doing independent research as early as possible. If you’re in a lab that you don’t like, then switch. That will also give you experience with seeing different mentoring styles. In undergrad, it’s a lot easier to change which lab you’re in after a year if needed, but when you’re getting your Ph.D. you commit 4-6 years to one lab. I should also mention: You want to make sure you’re doing the science that you like and  that you’re with a boss that you like. That’s something that isn’t always talked about–it’s not just what type of science you’re doing, it’s who you’re working for and with.

Finally, be ready to work really, really hard. Nine to five doesn’t mean anything here–you work whenever you’re awake. So know that if you’re going to do a Ph.D. in science, you have to truly love it.