Saturday, March 21, 2009

Do you choose the research, or does the research choose you?

Note: I give advanced warning to my non-biologist readers that the next few paragraphs below contain a good dose of biology. While I have attempted to keep it conversational, if you feel your eyes glazing over, skip down a few paragraphs for the real meat.

to the air

Yesterday (Friday) I attended a talk by Susan Gottesman about small non-coding RNAs (sRNAs) and how they are involved in protein degradation. At this point in her esteemed career, Gottesman's best known work revolves around a particular Escherichia coli sigma factor—a protein responsible for transcription—called RpoS. RpoS facilitates translation of messenger RNAs (mRNAs) into proteins at low temperature levels. Now, RpoS only appears in E. coli cells during low temperature conditions, but mysteriously (or so it was), the gene that encodes RpoS gets expressed even when the cells are growing at a comfortable temperature.

As Gottesman's lab discovered, the mRNA for RpoS can actually bend back around and stick to itself such that ribosomes aren't able to bind to the mRNA and translate it into the RpoS protein. An sRNA called DsrA, however, which is expressed in low temperature conditions, binds to part of the RpoS mRNA, preventing the mRNA from folding back on itself, and giving ribosomes access to the transcript to translate it into RpoS protein. Why is this important?

Well, previously, sRNAs had only been thought to inhibit translation and prevent proteins from appearing. That is, we say that sRNAs usually inhibit the expression of a protein, so if you found an sRNA, you would bet that its target wouldn't appear when it appeared. Add sRNA and the protein won't be found in the cell; take the sRNA away, and the protein re-appears. The Gottesman lab, however, demonstrated a case where the sRNA actually is responsible for making the proteins appear. That is, when the sRNA DsrA appears, its target, RpoS, appears too; and if you take away DsrA, the protein goes away, too! Craziness! In Biology, we call this a paradigm shift. Paradigm shifts are "big deals", because Biology is all about figuring out the rules, and then identifying the exceptions so we have to re-write the rules. Biology is the science of exceptions.

The story continues, but I'll leave it to the reader to check out Gottesman's publications for more, because as much as I liked the story of her research, what I found most interesting about the talk was this side comment that she made towards the end, which I paraphrase here:

We published this work with RpoS, but then we wanted to work in other directions. We'd try something, then discover we couldn't go in that direction because we needed to know something else about RpoS. Then we'd attempt something else, but again, it would always come back to RpoS. Finally we just said, "Forget it! Fine! We'll just study RpoS. Clearly there's enough here to work on for a while."
I don't know if the fellow grad students in the audience caught the subtle significance of this statement, or if perhaps I was the only person who found this significant. What Gottesman said, in more words, is that she didn't really choose her research; her research chose her. Yet, in spite of spending her career in an area she never intended to stay in, once she identified that she was mired in it, she made the best of it, leading to great scientific contributions and earning her accolades and prestige that even the most jaded of us junior researchers catch ourselves fantasizing about from time to time.

I find this significant because, also from time to time, I wonder how the researchers, and even my peers, that I have come to admire wound up doing the research that they're doing. In my earlier days, I often thought they must possess great foresight and wisdom. While I don't doubt they're clever people, the longer my tenure in research and the more people I harass to tell me about their own careers, the more I've begun to think that a lot of it just comes by chance rather than deliberate choice. We find ourselves in a particular unique positions, somewhat stuck, and somewhat stumped, and we throw up our hands and say, "Aw, Hell! I guess I might as well dig around while I'm here." We do have to make choices about where we dig, but we seem to get to choose our own particular holes about as well as seeds scattered by the winds. (Though, from time to time, we can try to ride the winds to another hole.)

I suppose that I just find it amusing that life is stochastic from the molecular level all the way up to our own grand plans. Like each of our cells, we may as well just deal with the cards we're dealt as best we can. For everything else... well, "Cast Your Fate to the Wind".

1 comment:

  1. Interesting post. Found you via @Berci on twitter. I think this research chooses you phenomenon is somewhat unique to the biological sciences and demonstrates the vastness of what we still don't understand. Biological systems are so complex and in a constant state of change that there will always be new things to discover, no matter what your starting point is.