July 24, 2007

Biting off more than one can chew

Posted by Eric at 10:43 am | Category: Academia, Personal, Science

Part of the problem with looking at a field like computational biology or systems biology (which I have some interest in) is that it’s hard to figure out how to narrow the field into one project that I can do for graduate school.

In synthetic organic chemistry, this was a relatively easy proposition. Pick a molecule, not too big, not too small, with interesting complexity, and make it. Then you’re done with your Ph.D. (course, this is much easier said than done). In traditional biochemistry, molecular biology, or cell biology, you’d focus on one protein, one pathway, one set of activities, one phenotype, and then figure out what they do, how they interact, what affects them, etc. When you generate enough publications and have a good, detailed story to tell about the systems, you’re done.

But computational biology feels like a whole ‘nother thing. It’s probably because I’m still not quite as familiar with that field, but it seems very methodological, more than anything else, and so it’s hard to find a particular angle to break down the problem and get a story out of it for a thesis. There’s not just one specific model system to work on, or one biochemical system that one can mine. At some point, it feels a little arbitrary, that you choose a system hoping that your hammer will find a nail you can hit; it could be that you choose wrong and just get screwed (I couldn’t help myself with that pun).

I remember reading about Eugene Shakhnovich’s work on protein folding, and he always had a particular angle to hit the topic with: his lattice folded proteins. One of the professors that I talked to at my new university tends to focus on bacterial chemotaxis. I need a good focus point by which to approach the field. Large-scale topics for data-mining, such as the ENCODE project, just seem too big for me to do as part of my Ph.D. project, and it would probably make my Ph.D. drag on and on in a way that would both make me depressed and make my work harder.

Perhaps I can find a particular algorithm to work on, if I decide to do a “big biology” sort of project. A particular technique, perhaps? I feel like doing a particular methodology is the only manageable way to approach “looking at systems-level behavior.” Otherwise, you’re relying on luck (pick a system and hope you can use your hammer). Because systems biology isn’t really a field, right? It’s just a methodology.

Maybe that’s why people like the reductionist mode of research so much? At least it’s easy to find a story to tell. I guess it’s a little like history. Everyone wants a handle, some sort of focal point. So you get focal points, like Alexander the Great, or Napolean. Even when studying social trends and situations, such as poverty and crime, you get the Italian Mafia, Tammany Hall, Five Points. Focal points.

So here I am, trying to wade through the literature and find a good focus.

4 Responses to “Biting off more than one can chew”

  1. JAJansenJr Says:
    July 24th, 2007 at 10:26 pm

    Pick a project involving a particular protein which is well understood and find a way to measure how it folds. Then relate this known folding pathway to an algorithm which uses the molecular forces involved in the folding steps. Much of what is currently being done computationally is semi-empirical and not likely to be of lasting significance. It is a hugely complicated problem but attacking a particular folding problem and coming up with an excellent understanding is worth striving for.

  2. Hugh Says:
    July 24th, 2007 at 10:29 pm

    You are right - systems biology is simply a series of tools. Simply put, you should find a project you are interested in then find out all the relevant physiology and biochemistry. Then pick an angle and go for it. Chemotaxis is one such topic - pretty cool stuff (and one of the major “systems” people, Uri Alon, got his start in it). You will need a story at the end of your PhD to be satisfied, not just a massive list of genomic, proteomic and/or microarray crap that will tell you nothing.

  3. Eric Says:
    July 24th, 2007 at 11:06 pm

    Didn’t realize Uri Alon started so “small” scale, considering the stuff he’s doing now. I love his group’s work, though.

    JAJansenJR: I’m not as much into the structural biology/molecular mechanics side of computational biology; I’m not sure I could stomach more work on orbitals and bond-strength modeling, having taken five courses on p-chem. :-P But thanks! It does sound like an interesting tack for someone who’d do protein folding.

  4. Pedro Beltrao Says:
    July 25th, 2007 at 10:11 am

    Maybe network reconstruction problems ? How to combine different datasets to predict the underlying pathways. If you like genome analysis than metagenomics probably needs a lot of new tools. Also in genomics, the personalized medicine part is maybe interesting. There is a lot of incoming data on genetic variation maybe associated with other data like gene expression, gut microbial sampling and disease information.

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