Thoughts on Theses: Yanzhen Lu
Issue   |   Wed, 02/03/2016 - 01:27

Yanzhen Lu is a biochemistry and biophysics major on the biochemistry track. Her thesis focuses on the activity of different forms of the protein HePTP. Her adviser is Professor of Chemistry Anthony Bishop.

Q: What is your thesis about?
A: The essence of my thesis is that I’m doing a detailed case study for a protein, HePTP, and two of its mutants. In humans, it has been implicated in diseases, such as lymphoma and other diseases that have to do with the thymus, which is where this protein is found. I’ll be comparing their characteristics, such as their activity and their response to inhibition by a small molecule called FlAsH, in detail.

Q: What was your procedure for doing this?
A: To do this, I first had to grow bacteria to express the protein, [and then] I purified it. [Protein expression is] growing bacteria that will express the protein. It grows overnight, but I have to do different things. I have to grow a liquid culture, and then I dilute it back into the main culture. The cells have to grow until they reach critical density, and then I stop the growth because that’s when it’s the best time to measure. I’m trying to isolate the protein that I want so I can study it. To figure out the concentration of the protein, I did Bradford assays, activity assays, and inhibition assays, so a bunch of assays. The final goal is to send the proteins off to be DNA sequenced so that we can confirm that the proteins are what we expect. We’re hoping that the mutants have similar activity to the wild type, but unlike the wild type, they’ll hopefully be sensitive to inhibition. We want to know if that can be achieved by modifying the DNA sequence of the protein.

Q: Why did you choose this experiment—what was the background on it?
A: Professor Bishop assigned me a project that he thought would be interesting for me to do and I agreed. A previous student was working with this protein and she found this site [on the protein] that was susceptible to mutagenesis.

Q: Have you seen any results? What are possible applications of these results?
A: I’ve [seen] a few preliminary results. I’d only actually done tests for ... the wild type, and it seems to have good agreement with what’s been reported in the literature in terms of its activity level. It has some implications for ... changing the DNA sequence because the wild type form of this protein is found in humans and it’s been implicated in some diseases. If we can successfully mutate a protein so that it has some of the same characteristics as the wild-type ... we can change how that protein affects the human body.

Q: What were some of the difficulties you encountered?
A: One of the difficulties was [that] one certain mutant wasn’t expresasing properly. I’ve been struggling with determining the concentrations of one of my protein mutants. I ran a bunch of gels and the results were inconsistent, so I’ve been talking to my adviser. I’m still in the lab phase. I guess the hardest part of the lab phase is that sometimes experiments don’t give you the results you expect, so having to think about what might be behind that is a challenge. I think the hardest part of the entire thesis experience will be the writing portion.

Q: So far, what parts of writing your thesis have been easy or enjoyable?
A: I definitely like going to lab and when I do get results, it’s very satisfying when something works right. It’s also a lot of fun doing background reading. I try to be in the lab every day because it’s good to get in the routine of going every day. Even if I’m not doing benchwork, I can still read and write. It’s been really cool to work with a faculty member, one-on-one. What’s also kind of fun and encouraging is, if you’re not the only thesis student in your lab, we keep each other motivated.

Q: How has this research impacted your academic and research goals?
A: It’s reaffirmed for me that yes, this is what I want to do, so I’m pretty happy. It is pretty interesting to go into lab and work with this protein and also to read on what others have written about it. I asked myself if this was something I could see myself doing after five, ten, twenty years, and the answer is yes. I eventually plan to go to graduate school, so doing a thesis will be a huge stepping stone to that, but I don’t think I’ll be sticking with the same topic. I do hope to get it published in a journal. My adviser did tell me something along the lines of, it would be difficult to argue your way into grad school without having done a thesis or some kind of significant research experience.

Q: What are your general research interests, and how does your thesis research play into that?
A: For me, genetics has always been really interesting, and although I might not spend the rest of my life studying this particular protein, it’s definitely paved the way for research in similar fields.

Q: If you could talk to yourself before you began your thesis, what would you say?
A: I think I would’ve questioned myself a lot more, like why I wanted to do a thesis. I’m happy I’m doing one. I think I would’ve told myself to be more mentally prepared. Definitely don’t underestimate how much work a thesis is.

Q: Why are you a biochemistry and biophysics major?
A: I pretty much wanted to be a scientist since I was little. My adviser is Professor Anthony Bishop. I think I wanted to work in his lab because I saw potential there for editing a protein sequence, which ties into genome editing, and I thought it was really interesting.

Q: What would you tell future BCBP majors interested in writing a thesis?
A: Just be sure you can really dedicate yourself to it. You have to really enjoy what you’re doing and be passionate and motivated. I wish I had gotten a head start on writing and planning the thesis last semester, because I’m realizing now that I only have a few months before it’s due. I started in the summer and I found that really helpful, just to have extra time to work on my thesis, because without courses and extracurriculars, it was really helpful just to be able to focus on that every day. The process of writing a thesis is really great in that you get to work really closely with a faculty member and build a relationship with them. I’ll definitely keep in touch after I graduate, and I think the connections I make at Amherst will serve me well after graduation. Know that things aren’t going to go the way you want, and definitely allow for some flexibility in the way you do things.

This interview has been edited and condensed for clarity.

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