The Dark Secret of Bioinformatics

Last week, I gave a presentation on my current research. My brief introduction ended with comments that are a mantra to many grad students: “…which will hopefully be my dissertation project.” The talk went well enough—the audience was just other grad students—and I got a lot of good feedback. At the start of the question-and-answer period, one of the girls raised her hand and asked, “Do you have a hypothesis?”

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Sleeping Mitra

Sleeping Mitra

Advance to Candidacy, Collect $200

Yesterday, you were reading the mad ramblings of a mere graduate student. Today, you are reading the mad ramblings of an official PhD candidate. Woohoo!

Unfortunately, I didn’t actually get any money. Doh!

I’m really quite pleased with this. A lot of my troubles in grad school have come from a lack of a clear plan, but now I have one. And it’s not just my own crazy, hare-brained ideas; it has actual faculty input. I feel like I should have done this a year ago. But then, who knows what my project would be or if that really would have avoided any of the turbulence of the last year. Certainly the genomes that are central to my project weren’t available then.

A Modest Proposal

There comes a time in every grad student’s life when he must propose a dissertation topic, and that time is finally upon me. It has been astoundingly difficult for me to figure out exactly what is involved in making a proposal, and I can’t decide if that’s due to miscommunication, benign neglect, or design.

When my class had our qualifying exams last year, there was big meeting and everything was laid out for us pretty clearly. There has been no such meeting for proposals, which makes sense because it’s a much smaller deal than quals (though no less necessary for attaining the Ph.D.). My first inclination to explain my own lack of information is to think that my boss expects the department staff to tell us about it while the staff expects my boss to handle it—miscommunication. It’s equally likely that no one realizes I’m adrift—benign neglect. (I have tried a couple of times to arrange meetings with my professor to get this straightened out, but he seems oblivious to my confusion.) My sneaking, paranoid suspicion is that we students are intentionally left in the dark. The Ph.D. is supposed to teach us to be independent researchers, so why not leave it up to us to take the final steps to becoming doctoral candidates on our own?

I think that’s giving the faculty too much credit; they have better things to do than actively trying to make our lives difficult. And lest anyone get the wrong impression, I’m really just amused—not upset—by these circumstances, at least since I found the answers and got them confirmed by the department’s staff. It’s just par for the course for grad school. See Piled Higher and Deeper for more evidence.

I’ve taken the structure for my dissertation proposal from my grad school bible, Getting What You Came For, which suggests a three-part format. The proposal starts with a brief introduction and then lays out the research problem. This is followed by a review of all of the relevant literature and an in-depth description of the research methods and techniques that will be used. The format could just as easily have been stolen from the NIH R01 grant, which follows a similar pattern.

My great epiphany from this experience is that no research project should be undertaken without a proposal. It doesn’t have to be as grandiose as even the ten-page proposal I’m preparing for my dissertation, but it should contain all the same parts: a clear statement of the problem, the questions involved, and the goal or end result of the project; a review of the literature; and a clear description of the techniques that will be used. In a perfect world, it should also include a timeline and milestones. This proposal (perhaps without the lit review, which can be very time consuming) should be circulated and agreed to by all involved parties.

Too often I feel like I have floundered in my own endeavors because I didn’t fully understand the project that I was working on. I didn’t have a larger context to put it in. I didn’t have a clear idea of the project’s goal or expected result. Having a clear proposal for each project would have helped tremendously, and it’s something I intend to do for new projects going forward.

Goals

Last time, I said that I had clear vision of my future. I want to lay that out now, as much for my benefit as anyone else’s. I want to work in systems biology. I’m really interested in the range of interactions within a cell, and I want to contribute to applying results from high-throughput studies, such as microarray analysis, to real biological problems, primarily cancer and other diseases.

Wow, this has really turned into a personal mission statement. I’ve also realized that while I’m not currently working on anything that could even loosely be termed “systems biology,” I am studying cellular interactions, so at least I’m kinda on course.

Wikipedia is telling me there’s something called “computational systems biology,” which nominally sounds like it’s right up my alley. But when it comes down to it, I’m much more interested in applications than in pure research. So if I need to develop new algorithms, then that’s great, but if I just need to process data, then so be that’s great, too, so long as my efforts are contributing meaningfully to the research.

I’m also interested in synthetic biology, but there are two problems with pursuing this area immediately. One is that it’s still a very bench-oriented enterprise. I don’t think we’ll ever get away from that as there are just too many random factors to handle computationally. Second and more significant, it’s still a very academic discipline, and I don’t want to be an academic. I think that systems biology now will pave the way for me to enter synthetic biology later, when it becomes a field in which biotech and pharmaceutical companies are interested.

I’m very interested in working at Genentech. The biotech company was just named as the best place to work by Fortune and as one of the top twenty smartest companies by Baseline. The Fortune article sacred me off a little bit, just because I wasn’t sure if I had the passion. But after writing this little “personal mission statement”—as touchy-feely as that sounds—I’ve found that I do.

Epiphany

Sometimes I have a very hard time getting motivated about my research. I don’t have any problem doing homework for my classes, and once I get into my research, it’s fine. It’s just sometimes I can’t seem to find the energy to get started. I had thought that maybe this was a sign that I’d perhaps made a bad decision somewhere along the line, but I realized the other day that the source of my anxiety is not my research, it’s my career after grad school.

For a long time, I didn’t have a clear vision of what I want to do after graduation and after my post-doc. I do now. But it’s still not always clear to me how to get from here to there. Part of the problem is that I feel like a career in science doesn’t follow a clear progression. While that can be true of any job, I feel like it happens far more often than not in science careers. Or maybe I just feel like things never work out for me the way I want them to.

Really, I need to be doing everything I can now to stack the deck in my favor. I know where I want to be in two years (when I’m doing my post-doc) and in four (or whenever the “real” job starts). So I need to make sure that the path I’m on now gives me the best chance to make that vision a reality.

I’ve started doing some of that. My in-laws provided me with a contact at GlaxoSmithKilne, who provided me with another. I’ve also been in touch with a researcher at Genentech. All three have been very helpful. However, I need to do some more research and make more contacts.

I think that, at least until I get established, I will always have some anxiety about my career. Doing this sort of due diligence will take some effort and it will take me out of my comfort zone, but it will be worth it, especially as it will help me achieve my goal. Certainly, I feel more confident now about my career than I have in a long time.

I Hate Science

Ok, I don’t actually hate science, but I certainly feel that way sometimes when doing experiments. Here’s an example. In my system, I have some RNA (an aptamer, in fact) that has been labeled with a fluorescent dye. I also have a shorter piece of DNA that is complimentary to the aptamer, so it will bind to the aptamer. The DNA is labeled with a quencher that prevents the dye from emitting its signal. Basically, when the DNA is present, the aptamer doesn’t glow, and when the DNA is absent, it does glow.

At least, that’s the way it should work. In some of my experiments, the more DNA I added, the brighter the aptamer glowed. This is the exact opposite of what should happen. It’s like the TV turning off when you press the on switch, only you can’t blame it on faulty wiring. Maybe it’s more like water flowing uphill, since these are basic physical properties of matter we’re talking about.

Nonetheless, it’s very frustrating. Fortunately, that project was canceled recently, due in part to the confounding results I was getting.

I’ve been having some trouble getting back on track with my other projects. I’m not sure why, exactly. Sometimes simply having to do something makes it unappealing, no matter how interesting it might be if it weren’t a requirement.

But in the last few days, I’ve felt really on top of things. I’ve been very productive. I worked on my mountain bike and have gone on a few short rides. I’ve taken care of various projects around the house. I’ve even made some progress on my main research project. Hopefully, I can keep things on track and maintain my forward momentum.

Plus, I always have Piled Higher and Deeper to console me in any event.

Motivation

I’ve been on a major slump lately, as far as my research goes. Everyone traditionally has a post prelim period where they don’t get much done, but this has lasted for months. I just am not very excited about my current project, but it hasn’t been clear to me exactly why I’m not excited.

I guess part of it is that the research doesn’t seem to present any particular challenge, because it seems clear to me that it will work. I also don’t really see where it’s going, what the larger implications are. So we’ll be able to predict X, Y, and Z. That’s useful, but what can I do with it at that point? Not much.

I did experience a brief swell of enthusiasm when it was time to start moving from the computational phase to the experimental portion, simply because I’ve hardly done any bench work in grad school. But that faded, too, especially as even ordering the chemicals I need has become a headache.

But I found myself quite elated yesterday when I had an idea for an experiment to make a synthetic goober, which is how Andy likes to refer to my aptamer designs. What I realized is that last year, when I had my own research, I was really excited about the implications and possibilities of it, even if we were in the very earliest stages. I could see that it had a future, and it was a tantalizing vision that I wanted to be a part of. Thus far, I haven’t had that sort of feeling about my current project. Now I kinda of do, so today, I’m a little more motivated and a little more excited.

Nonetheless, I need to find a second project to work on, if only to avoid putting all my eggs in one basket.

Go me

I won an IGERT Fellowship. The program is administered locally at UT, but the funds come from the National Science Foundation or some other federal group. Funding is for 2 years. I’m not sure how many people applied (there are at least two people in my lab who didn’t get it), but they only select six each year. Free money. I love it.

crazy science people